Pub Date : 2022-07-14DOI: 10.31487/j.rgm.2022.01.01
N. Niazi, J. Wong, A. Pillai
Introduction: Post-traumatic subtalar joint arthritis is uncommon and the majority results as a consequence of either an intra-articular calcaneal or talar fracture. A unique case of management of subtalar joint arthritis is described using autologous microfragmented adipose cells therapy. Case Report: We presented a 48-year-old male with symptomatic left subtalar joint arthritis, which was managed conservatively with analgesia and multiple steroid injections. During surgery, fat cells were aspirated from the abdomen and transferred to the Lipogems kit for mechanical breakdown of adipose tissue for around 20 minutes. Final 10ml of the product was injected into the subtalar joint. Patient was followed up at regular intervals and Visual analogue score (VAS), Manchester-Oxford Foot Questionnaire (MOXFQ) and Foot and Ankle Ability Measure scores (FAM-ADL) were collected. Results: No perioperative complications were noted relating to abdominal liposuction and intra-articular injection of lipoaspirate and during the follow-up period. Improvement in VAS, MOX FQ and FAM-ADL scores was noted up to 6 months of follow-up. Discussion: The subtalar joint plays a central role in load transmission and movement at the hindfoot and its malalignment and arthritis lead to impaired function and pain. Intra articular injections of fat cells and their regenerative potential in degenerative joint diseases have been well documented in literature. Lipogem technique has been used in knee, hip and ankle arthritis, but it is not documented to use in the subtalar joint. Conclusion: This unique case report demonstrated the successful use of a single-dose autologous micro fragmented fat cells therapy leading to functional improvement in subtalar joint arthritis with no complications.
{"title":"Autologous Micro Fragmented Adipose Cells Therapy for Subtalar Joint Osteoarthritis – Case Report and Review of Literature","authors":"N. Niazi, J. Wong, A. Pillai","doi":"10.31487/j.rgm.2022.01.01","DOIUrl":"https://doi.org/10.31487/j.rgm.2022.01.01","url":null,"abstract":"Introduction: Post-traumatic subtalar joint arthritis is uncommon and the majority results as a consequence of either an intra-articular calcaneal or talar fracture. A unique case of management of subtalar joint arthritis is described using autologous microfragmented adipose cells therapy.\u0000Case Report: We presented a 48-year-old male with symptomatic left subtalar joint arthritis, which was managed conservatively with analgesia and multiple steroid injections. During surgery, fat cells were aspirated from the abdomen and transferred to the Lipogems kit for mechanical breakdown of adipose tissue for around 20 minutes. Final 10ml of the product was injected into the subtalar joint. Patient was followed up at regular intervals and Visual analogue score (VAS), Manchester-Oxford Foot Questionnaire (MOXFQ) and Foot and Ankle Ability Measure scores (FAM-ADL) were collected.\u0000Results: No perioperative complications were noted relating to abdominal liposuction and intra-articular injection of lipoaspirate and during the follow-up period. Improvement in VAS, MOX FQ and FAM-ADL scores was noted up to 6 months of follow-up. \u0000Discussion: The subtalar joint plays a central role in load transmission and movement at the hindfoot and its malalignment and arthritis lead to impaired function and pain. Intra articular injections of fat cells and their regenerative potential in degenerative joint diseases have been well documented in literature. Lipogem technique has been used in knee, hip and ankle arthritis, but it is not documented to use in the subtalar joint.\u0000Conclusion: This unique case report demonstrated the successful use of a single-dose autologous micro fragmented fat cells therapy leading to functional improvement in subtalar joint arthritis with no complications.","PeriodicalId":148803,"journal":{"name":"International Journal of Regenerative Medicine","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114577405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-02-03DOI: 10.31487/j.rgm.2021.02.04
N. Niazi, A. Aljawadi, M. Khan, A. Pillai
Achilles tendon rupture is one of the most common tendon injury in adult population. Synthetic ligament has been an attractive alternative for reconstruction chronic Achilles tendon tears. Ligament reconstruction with the LARS ligament has been a popular choice owing to its low-complication rates. LARS ligament is a non-absorbable synthetic ligament device. There are no long-term results of LARS ligament reconstruction for Achilles tendon reconstruction in literature. We describe a successful management of foreign body granuloma in a LARS ligament Achilles tendon graft and a technique to reconstruct the tendon following its excision.
{"title":"Foreign Body Reaction with Granuloma 10 Years After Achilles Tendon Reconstruction with the LARS Ligament","authors":"N. Niazi, A. Aljawadi, M. Khan, A. Pillai","doi":"10.31487/j.rgm.2021.02.04","DOIUrl":"https://doi.org/10.31487/j.rgm.2021.02.04","url":null,"abstract":"Achilles tendon rupture is one of the most common tendon injury in adult population. Synthetic ligament has been an attractive alternative for reconstruction chronic Achilles tendon tears. Ligament reconstruction with the LARS ligament has been a popular choice owing to its low-complication rates. LARS ligament is a non-absorbable synthetic ligament device. There are no long-term results of LARS ligament reconstruction for Achilles tendon reconstruction in literature. We describe a successful management of foreign body granuloma in a LARS ligament Achilles tendon graft and a technique to reconstruct the tendon following its excision.","PeriodicalId":148803,"journal":{"name":"International Journal of Regenerative Medicine","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129052346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-12-20DOI: 10.31487/j.rgm.2021.02.03
A. Gennai, B. Bovani, M. Colli, F. Melfa, D. Piccolo, R. Russo, B. Roda, A. Zattoni, P. Reschiglian, S. Zia
Background: Clinical studies demonstrated the efficacy of therapies based on the autologous grafting of adult mesenchymal stem cells to accelerate the healing and regenerative processes of the skin and mesenchymal tissues; therefore, it is considered a valuable approach in the aesthetic rejuvenation treatment to give volumization and skin regeneration effects. Objective: The aim of the project consisted of the control of cell viability of adipose tissue (AT) harvested using the two types of cannulas having 0.8 mm and 1 mm side port holes. The results were compared with tissue harvested with a standard liposuction technique and processed with a standard procedure consisting of enzymatic digestion (collagenase). Methods: This study was performed on adipose tissues harvested from 7 patients (6 females and 1 male) with an average age of 48.5 years with 3 different techniques. We compared the cell vitality of every sample at T0 and T72. Results: Lipoaspirate tissue-derived by 0.8- and 1 mm cannula from all samples proved to be vital and possess viable cells. The average absorbance was similar immediately after plating (T0) and 72 hours after (T72) for the two cannulas, 0.8- and 1 mm cannula. The two systems proved to equally harvest vital tissue. An increase in cell viability was observed in all samples for each condition (0.8-, 1 mm and enzymatic digestion). Conclusion: This study proved that guided harvested adipose tissue with small cannulas with small side port holes yields a comparable amount of viable cells compared to adipose tissue harvested with a liposuction system and processed with enzymatic digestion (collagenase). This study confirms that the minimally invasive technique and minimal manipulation of the adipose tissue could yield a tissue with a good amount of viable cells. This micro fragmented adipose tissue is a promising source for regenerative treatments.
背景:临床研究表明,基于自体移植成体间充质干细胞的治疗方法可以加速皮肤和间充质组织的愈合和再生过程;因此,它被认为是一个有价值的方法,在美容年轻化治疗,以提供体积和皮肤再生的效果。目的:研究采用侧孔为0.8 mm和1mm的两种套管采集的脂肪组织(AT)细胞活力的控制。将结果与标准吸脂技术收获的组织进行比较,并使用由酶消化(胶原酶)组成的标准程序进行处理。方法:采用3种不同的技术,对平均年龄48.5岁的7例患者(6例女性,1例男性)的脂肪组织进行研究。我们比较了每个样品在T0和T72时的细胞活力。结果:从所有样本中提取的由0.8 mm和1mm套管提取的抽脂组织被证明是有生命的,并具有活细胞。0.8 mm和1mm套管的平均吸光度在镀后即刻(T0)和72小时(T72)时相似。事实证明,这两种系统同样能收获重要组织。在每种条件下(0.8 mm, 1 mm和酶消化),所有样品的细胞活力都有所增加。结论:本研究证明,与用吸脂系统采集并经酶消化(胶原酶)处理的脂肪组织相比,用带小侧孔的小套管引导采集的脂肪组织产生的活细胞数量相当。本研究证实,微创技术和对脂肪组织的最小操作可以产生具有大量活细胞的组织。这种微碎片脂肪组织是再生治疗的一个有希望的来源。
{"title":"Comparison of Harvesting and Processing Technique for Adipose Tissue Graft: Evaluation of Cell Viability","authors":"A. Gennai, B. Bovani, M. Colli, F. Melfa, D. Piccolo, R. Russo, B. Roda, A. Zattoni, P. Reschiglian, S. Zia","doi":"10.31487/j.rgm.2021.02.03","DOIUrl":"https://doi.org/10.31487/j.rgm.2021.02.03","url":null,"abstract":"Background: Clinical studies demonstrated the efficacy of therapies based on the autologous grafting of adult mesenchymal stem cells to accelerate the healing and regenerative processes of the skin and mesenchymal tissues; therefore, it is considered a valuable approach in the aesthetic rejuvenation treatment to give volumization and skin regeneration effects.\u0000Objective: The aim of the project consisted of the control of cell viability of adipose tissue (AT) harvested using the two types of cannulas having 0.8 mm and 1 mm side port holes. The results were compared with tissue harvested with a standard liposuction technique and processed with a standard procedure consisting of enzymatic digestion (collagenase).\u0000Methods: This study was performed on adipose tissues harvested from 7 patients (6 females and 1 male) with an average age of 48.5 years with 3 different techniques. We compared the cell vitality of every sample at T0 and T72.\u0000Results: Lipoaspirate tissue-derived by 0.8- and 1 mm cannula from all samples proved to be vital and possess viable cells. The average absorbance was similar immediately after plating (T0) and 72 hours after (T72) for the two cannulas, 0.8- and 1 mm cannula. The two systems proved to equally harvest vital tissue. An increase in cell viability was observed in all samples for each condition (0.8-, 1 mm and enzymatic digestion).\u0000Conclusion: This study proved that guided harvested adipose tissue with small cannulas with small side port holes yields a comparable amount of viable cells compared to adipose tissue harvested with a liposuction system and processed with enzymatic digestion (collagenase). This study confirms that the minimally invasive technique and minimal manipulation of the adipose tissue could yield a tissue with a good amount of viable cells. This micro fragmented adipose tissue is a promising source for regenerative treatments.","PeriodicalId":148803,"journal":{"name":"International Journal of Regenerative Medicine","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127063075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-10-21DOI: 10.31487/j.rgm.2021.02.02
A. Gennai, B. Bovani, M. Colli, F. Melfa, D. Piccolo, R. Russo, M. Tretti Clementoni, S. Zia, B. Roda, A. Zattoni
Background: Injection of autologous adipose-derived stem cells (ADSCs) and a stromal vascular fraction (VSF) into dermal and subdermal layers promises regenerative advantages by improving skin volume and rejuvenation. Injectable hyaluronic acid (HA) is a temporary dermal filler that, by improving skin hydration, reduces the appearance of fine lines and wrinkles, facial folds and creates structure and volume to the face and lips. This study combined the grafting of micro fragmented fatty tissue with the hyaluronic acid filler procedure, using three different types of HA. Methods: Each sample of micro fragmented adipose tissue harvested using the superficial enhanced fluid fat injection (SEFFI) technique collected from 8 patients were equally divided into two specimens. One of these (EMU specimens) was emulsified by gently applying ten back-and-forth passages from one syringe to another to fluidify the tissue. The other one was not emulsified (Ctrl/NON-EMU specimen). Both EMU and NON-EMU specimens were divided into four aliquots: one served as control, and the others were combined with each of three tested hyaluronic acids. Afterward, we assessed the cellularity of mesenchymal phenotype (defined as the number of adherent cells with mesenchymal phenotype per milliliter of adipose tissue) and the in vitro capacity of differentiation in mesenchymal lineages. Results: Despite low cellularity from emulsified samples combined with HA, isolated cells could grow and expand in culture, thus proving their proliferative ability, showing “good quality” in all conditions (Ctrl/NON-EMU, EMU, and combined with HA). The cells could differentiate towards mesenchymal lineages, express mesenchymal markers by flow cytometry analysis, and maintain their stemness potential. Conclusion: The combination of emulsified harvested tissue with HA products can be exploited to counteract the loss of volume and skin aging of the human face and body. This approach to regenerative aesthetic treatment is a promising treatment for facial antiaging therapy.
{"title":"Evaluation of the Number, Biophysical and Multipotent Characteristics of Adipose Derived Stem Cells Harvested by SEFFI Procedure and Interaction with Different Type of Hyaluronic Acids","authors":"A. Gennai, B. Bovani, M. Colli, F. Melfa, D. Piccolo, R. Russo, M. Tretti Clementoni, S. Zia, B. Roda, A. Zattoni","doi":"10.31487/j.rgm.2021.02.02","DOIUrl":"https://doi.org/10.31487/j.rgm.2021.02.02","url":null,"abstract":"Background: Injection of autologous adipose-derived stem cells (ADSCs) and a stromal vascular fraction (VSF) into dermal and subdermal layers promises regenerative advantages by improving skin volume and rejuvenation. Injectable hyaluronic acid (HA) is a temporary dermal filler that, by improving skin hydration, reduces the appearance of fine lines and wrinkles, facial folds and creates structure and volume to the face and lips. This study combined the grafting of micro fragmented fatty tissue with the hyaluronic acid filler procedure, using three different types of HA. \u0000Methods: Each sample of micro fragmented adipose tissue harvested using the superficial enhanced fluid fat injection (SEFFI) technique collected from 8 patients were equally divided into two specimens. One of these (EMU specimens) was emulsified by gently applying ten back-and-forth passages from one syringe to another to fluidify the tissue. The other one was not emulsified (Ctrl/NON-EMU specimen). Both EMU and NON-EMU specimens were divided into four aliquots: one served as control, and the others were combined with each of three tested hyaluronic acids. Afterward, we assessed the cellularity of mesenchymal phenotype (defined as the number of adherent cells with mesenchymal phenotype per milliliter of adipose tissue) and the in vitro capacity of differentiation in mesenchymal lineages.\u0000Results: Despite low cellularity from emulsified samples combined with HA, isolated cells could grow and expand in culture, thus proving their proliferative ability, showing “good quality” in all conditions (Ctrl/NON-EMU, EMU, and combined with HA). The cells could differentiate towards mesenchymal lineages, express mesenchymal markers by flow cytometry analysis, and maintain their stemness potential.\u0000Conclusion: The combination of emulsified harvested tissue with HA products can be exploited to counteract the loss of volume and skin aging of the human face and body. This approach to regenerative aesthetic treatment is a promising treatment for facial antiaging therapy.","PeriodicalId":148803,"journal":{"name":"International Journal of Regenerative Medicine","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121106196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-21DOI: 10.31487/j.rgm.2021.02.01
H. Wang, Ramesh R. Kaini, Christina L. Rettinger
Background: Human tissue/organ development is a complex, highly orchestrated process, regulated in part by the surrounding extracellular matrix (ECM). Every complex tissue, including the retina, has a unique ECM configuration that plays a critical role in cellular differentiation, adhesion, migration, and maturation. Aim: To characterize ECM expression of human induced pluripotent stem cell-derived optic vesicles (iPSC-OVs). Methods: A 3- dimensional (3D) in vitro suspension culture system was used to direct differentiation of human induced pluripotent stem cells (iPSCs) into optic vesicles (OVs). Stepwise differentiation of iPSCs into retinal progenitor cells was confirmed by sequential expression of OTX2, SOX1, SIX6, LHX2, PAX6, and CHX10. Expression of ECM genes in iPSC-derived OVs was analyzed by RT2 ProfilerTM PCR Array, whereas immunofluorescence staining was performed to detect ECM proteins in the OVs. Results: A number of cell adhesion molecules (CAMs) previously reported to be abundantly expressed in iPSCs such as E-cadherin, Intercellular adhesion molecule-1 (ICAM1), Integrin-α L, Integrin-α M, Integrin-α 6 were downregulated while neural and retina specific CAMs including neural cell adhesion molecule 1 (NCAM1), neural plakophilin-related armadillo repeat protein (NPRAP), Integrin-α 1 and Integrin-α 4 were upregulated. Several glycoproteins that have been reported to play key roles during retinogenesis, namely CD44, Tenascin C, Tenascin R, Neurocan, Neuroglycan C, Delta 2 Catenin, Vitronectin, and Reelin were also present. Conclusion: We have identified an array of ECM proteins that were expressed during retinogenesis. Further characterization of these proteins will lead to a better understanding of retinal development.
{"title":"Extracellular Matrix Expression in Human Induced Pluripotent Stem Cell-Derived Optic Vesicles","authors":"H. Wang, Ramesh R. Kaini, Christina L. Rettinger","doi":"10.31487/j.rgm.2021.02.01","DOIUrl":"https://doi.org/10.31487/j.rgm.2021.02.01","url":null,"abstract":"Background: Human tissue/organ development is a complex, highly orchestrated process, regulated in part by the surrounding extracellular matrix (ECM). Every complex tissue, including the retina, has a unique ECM configuration that plays a critical role in cellular differentiation, adhesion, migration, and maturation. \u0000Aim: To characterize ECM expression of human induced pluripotent stem cell-derived optic vesicles (iPSC-OVs). \u0000Methods: A 3- dimensional (3D) in vitro suspension culture system was used to direct differentiation of human induced pluripotent stem cells (iPSCs) into optic vesicles (OVs). Stepwise differentiation of iPSCs into retinal progenitor cells was confirmed by sequential expression of OTX2, SOX1, SIX6, LHX2, PAX6, and CHX10. Expression of ECM genes in iPSC-derived OVs was analyzed by RT2 ProfilerTM PCR Array, whereas immunofluorescence staining was performed to detect ECM proteins in the OVs. \u0000Results: A number of cell adhesion molecules (CAMs) previously reported to be abundantly expressed in iPSCs such as E-cadherin, Intercellular adhesion molecule-1 (ICAM1), Integrin-α L, Integrin-α M, Integrin-α 6 were downregulated while neural and retina specific CAMs including neural cell adhesion molecule 1 (NCAM1), neural plakophilin-related armadillo repeat protein (NPRAP), Integrin-α 1 and Integrin-α 4 were upregulated. Several glycoproteins that have been reported to play key roles during retinogenesis, namely CD44, Tenascin C, Tenascin R, Neurocan, Neuroglycan C, Delta 2 Catenin, Vitronectin, and Reelin were also present. \u0000Conclusion: We have identified an array of ECM proteins that were expressed during retinogenesis. Further characterization of these proteins will lead to a better understanding of retinal development.","PeriodicalId":148803,"journal":{"name":"International Journal of Regenerative Medicine","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134387645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-12DOI: 10.31487/J.RGM.2021.01.01
A. Gennai, P. Tesauro, M. Colli, S. Zia, B. Roda, A. Zattoni
Aim: The purpose of this article is to prove the possibility to transfer a good amount of cells of the SVF (and ADSCs) in the infranatant portion of microfragmented adipose tissue. Method: The adipose tissue harvesting procedure is performed under local anaesthesia. The adipose tissue was harvested with a 2 mm diameter microperforated cannula with 1 mm side port holes, mounted inside the special patented guide. Both cannula and guide are included in the SEFFIHAIR™ medical device. Once the adipose tissue is harvested, it is gently washed, and it was divided in two specimens: (EMU) the tissue was emulsified with 20 passages from one syringe to another and (CTRL) the tissue didn’t undergo any emulsification. Results: The emulsification procedure liberated alive and proliferating cells and we observed that the specimens derived with a 1 mm side port hole cannula and then emulsified (EMU) showed a higher number of cells in the infranatant part compared to the one derived from the control tissue without any (1 EMU vs. 1EMU infra). Conclusion: The use of microcannulas, in combination with a mechanical digestion by an emulsification procedure and centrifuge, could ease SVF cells isolation for regenerative treatment and could also be performed in a medical facility.
{"title":"Infranatant Portion of Microfragmented Adipose Tissue: A Promising Source of SVF for the Management of Androgenetic Alopecia","authors":"A. Gennai, P. Tesauro, M. Colli, S. Zia, B. Roda, A. Zattoni","doi":"10.31487/J.RGM.2021.01.01","DOIUrl":"https://doi.org/10.31487/J.RGM.2021.01.01","url":null,"abstract":"Aim: The purpose of this article is to prove the possibility to transfer a good amount of cells of the SVF\u0000(and ADSCs) in the infranatant portion of microfragmented adipose tissue.\u0000Method: The adipose tissue harvesting procedure is performed under local anaesthesia. The adipose tissue\u0000was harvested with a 2 mm diameter microperforated cannula with 1 mm side port holes, mounted inside\u0000the special patented guide. Both cannula and guide are included in the SEFFIHAIR™ medical device. Once\u0000the adipose tissue is harvested, it is gently washed, and it was divided in two specimens: (EMU) the tissue\u0000was emulsified with 20 passages from one syringe to another and (CTRL) the tissue didn’t undergo any\u0000emulsification.\u0000Results: The emulsification procedure liberated alive and proliferating cells and we observed that the\u0000specimens derived with a 1 mm side port hole cannula and then emulsified (EMU) showed a higher number\u0000of cells in the infranatant part compared to the one derived from the control tissue without any (1 EMU vs.\u00001EMU infra).\u0000Conclusion: The use of microcannulas, in combination with a mechanical digestion by an emulsification\u0000procedure and centrifuge, could ease SVF cells isolation for regenerative treatment and could also be\u0000performed in a medical facility.","PeriodicalId":148803,"journal":{"name":"International Journal of Regenerative Medicine","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115272053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-02-04DOI: 10.21203/RS.3.RS-182673/V1
Pawan Kumar Gupta, Anoop Chullikana, R. Seetharam, Udaykumar Kolkundar, P. ShivaShankar, Pachaiyappan Viswanathan, M. Chandrashekar, Charan Thej, K. Prasanth, Jijy Abraham, A. Majumdar
Background: Alcoholic liver cirrhosis is an end-stage alcoholic liver disease with a poor prognosis. The definitive treatment of alcoholic liver cirrhosis is orthotopic liver transplantation, which is expensive, requires long-term immunosuppression and is limited by the supply of organs. Being an unmet medical need, cell therapy is under investigation for alcoholic liver cirrhosis. Aims: This study was designed primarily for assessing the safety and feasibility of administering stempeucel® through the hepatic artery in alcoholic liver cirrhosis and secondarily to assess possible efficacy and dose-response. Methods: Sixty patients with alcoholic cirrhosis (18-65 years/Child-Pugh class B or C/Model for End-Stage Liver Disease score of minimum 10) were planned to be included in 6 groups: 2.5 million cells/kg Body Weight (2.5M Cell) and respective control (2.5M Control); 5 million cells/kg Body Weight (5M Cell) and respective control (5M Control); 7.5 million cells/kg Body Weight (5M Cell) and respective control (7.5M Control) with 10 patients in each group. Cell groups received stempeucel® administered via hepatic artery by catheterization through the femoral artery (Seldinger technique) and Standard Protocol of Care. The control group received Standard Protocol of Care. Patients were followed up at 1 week, 1 month, 3 months and 6 months. Efficacy evaluations included liver function test, Model for End-Stage Liver Disease score, Child-Pugh score, Short Form-36 questionnaire, liver stiffness using Fibroscan (Transient Elastography), and liver volume using Computerized Tomography scan. Results: Stempeucel® injection was well tolerated. Common treatment-emergent adverse events were gastrointestinal disorders, general disorders and administration site conditions and infections and infestations. Most of the treatment-emergent adverse events were unrelated / remotely related to stempeucel®. Thirty serious adverse events occurred in 10 patients (3 in 2.5M Cell, 5 in 5M Cell and one each in control groups). Three patients died due to SAEs: Two in 2.5M and one in 5M Cell group, none were related to stempeucel®. Statistically significant improvement was seen in 2.5M group compared to the control group in Short Form-36 score: bodily pain, mental component summary, vitality and social functioning. Conclusion: Stempeucel® was safe, well-tolerated and subjective improvement in Short Form-36 (bodily pain, mental component summary, vitality and social functioning and mental health) score was seen in the 2.5M cell group.
背景:酒精性肝硬化是一种预后不良的终末期酒精性肝病。酒精性肝硬化的最终治疗是原位肝移植,这是昂贵的,需要长期的免疫抑制,并受到器官供应的限制。作为一种未被满足的医疗需求,细胞治疗酒精性肝硬化正在研究中。目的:本研究的主要目的是评估经肝动脉给药stempeucel®治疗酒精性肝硬化的安全性和可行性,其次是评估可能的疗效和剂量反应。方法:60例酒精性肝硬化患者(18-65岁/Child-Pugh B级或C级/终末期肝病模型评分至少为10分)分为6组:250万个细胞/kg体重组(2.5 m Cell)和各自的对照组(2.5 m control);500万个细胞/公斤体重(5M Cell)及相应对照(5M control);750万个细胞/kg体重(5M Cell)和各自的对照组(750 m control),每组10例。细胞组接受stempeucel®经肝动脉经股动脉导管给药(Seldinger技术)和标准护理方案。对照组采用标准护理方案。随访时间分别为1周、1个月、3个月、6个月。疗效评估包括肝功能测试、终末期肝病模型评分、Child-Pugh评分、Short Form-36问卷、纤维扫描(瞬时弹性成像)肝脏硬度和计算机断层扫描肝脏体积。结果:Stempeucel注射液耐受性良好。常见的治疗不良事件是胃肠道疾病,一般疾病和给药部位状况以及感染和感染。大多数治疗中出现的不良事件与stempeucel®无关或有较远的关系。10例患者发生30例严重不良事件(2.5M细胞组3例,5M细胞组5例,对照组各1例)。3例患者死于SAEs: 2.5M组2例,5M细胞组1例,均与stempeucel®无关。与对照组相比,2.5M组在Short Form-36评分:身体疼痛、心理成分总结、活力和社会功能方面均有显著改善。结论:Stempeucel®安全、耐受性良好,在2.5M细胞组中Short Form-36(身体疼痛、精神成分总结、活力和社会功能以及心理健康)评分有主观改善。
{"title":"A Phase II Dose Escalation Study of Intraarterial (Hepatic) Adult Human Bone Marrow Derived, Cultured, Pooled, Allogeneic Mesenchymal Stromal Cells (Stempeucel®) in Patients with Alcoholic Liver Cirrhosis","authors":"Pawan Kumar Gupta, Anoop Chullikana, R. Seetharam, Udaykumar Kolkundar, P. ShivaShankar, Pachaiyappan Viswanathan, M. Chandrashekar, Charan Thej, K. Prasanth, Jijy Abraham, A. Majumdar","doi":"10.21203/RS.3.RS-182673/V1","DOIUrl":"https://doi.org/10.21203/RS.3.RS-182673/V1","url":null,"abstract":"Background: Alcoholic liver cirrhosis is an end-stage alcoholic liver disease with a poor prognosis. The definitive treatment of alcoholic liver cirrhosis is orthotopic liver transplantation, which is expensive, requires long-term immunosuppression and is limited by the supply of organs. Being an unmet medical need, cell therapy is under investigation for alcoholic liver cirrhosis.\u0000Aims: This study was designed primarily for assessing the safety and feasibility of administering stempeucel® through the hepatic artery in alcoholic liver cirrhosis and secondarily to assess possible efficacy and dose-response.\u0000Methods: Sixty patients with alcoholic cirrhosis (18-65 years/Child-Pugh class B or C/Model for End-Stage Liver Disease score of minimum 10) were planned to be included in 6 groups: 2.5 million cells/kg Body Weight (2.5M Cell) and respective control (2.5M Control); 5 million cells/kg Body Weight (5M Cell) and respective control (5M Control); 7.5 million cells/kg Body Weight (5M Cell) and respective control (7.5M Control) with 10 patients in each group. Cell groups received stempeucel® administered via hepatic artery by catheterization through the femoral artery (Seldinger technique) and Standard Protocol of Care. The control group received Standard Protocol of Care. Patients were followed up at 1 week, 1 month, 3 months and 6 months. Efficacy evaluations included liver function test, Model for End-Stage Liver Disease score, Child-Pugh score, Short Form-36 questionnaire, liver stiffness using Fibroscan (Transient Elastography), and liver volume using Computerized Tomography scan.\u0000Results: Stempeucel® injection was well tolerated. Common treatment-emergent adverse events were gastrointestinal disorders, general disorders and administration site conditions and infections and infestations. Most of the treatment-emergent adverse events were unrelated / remotely related to stempeucel®. Thirty serious adverse events occurred in 10 patients (3 in 2.5M Cell, 5 in 5M Cell and one each in control groups). Three patients died due to SAEs: Two in 2.5M and one in 5M Cell group, none were related to stempeucel®. Statistically significant improvement was seen in 2.5M group compared to the control group in Short Form-36 score: bodily pain, mental component summary, vitality and social functioning.\u0000Conclusion: Stempeucel® was safe, well-tolerated and subjective improvement in Short Form-36 (bodily pain, mental component summary, vitality and social functioning and mental health) score was seen in the 2.5M cell group.","PeriodicalId":148803,"journal":{"name":"International Journal of Regenerative Medicine","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129204410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-12-23DOI: 10.31487/j.rgm.2020.04.01
Zhipeng Yan, K. Cheung, Eric Ho-Yin Lau, Ching‐lung Lai
Background: Coronavirus Disease in 2019 (COVID-19) is a pandemic caused by SARS-CoV-2 infection. Over 53 million people have been infected with over 1.3 million deaths. However, there is no standard treatment or vaccines to date. Recently, several randomized controlled trials and cohort studies have demonstrated the efficacy of remdesivir for the treatment of severe COVID-19 patients. This is a systematic review and meta-analysis to define its efficacy. Methods: A systematic review was done on databases (PubMed, Embase, Medline, Cochrane) on 9 Nov 2020. Search keywords were remdesivir, COVID-19, SARS-CoV-2, randomized controlled trials and cohort studies. Studies with high-evidence values were selected to evaluate its clinical efficacy in terms of risk ratio, time to clinical improvement, and mortality risk. Subgroup analysis was performed based on baseline hospitalization status, age and ethnicity. Results: Of the 1328 studies, 6 studies were selected and pooled for meta-analysis. Remdesivir was associated with clinical improvement (risk ratio 1.14, 95% CI 1.02-1.28, p=0.02). It shortened the mean time of clinical improvement by 3.32 days (95% CI -4.37 to -2.28, p<0.001). However, its use was not associated with reduced mortality risk (risk ratio 0.75, 95% CI 0.40–1.40). In subgroup analysis, remdesivir was associated with clinical improvement in patients without the need of invasive ventilation (risk ratio 1.90, 95% CI 1.58-2.29, p<0.001; hazard ratio 2.22, 95% CI, 1.64-3.02), and age less than 70 years (risk ratio 2.14, 95% CI 1.39-3.28, p<0.001). Conclusion: Remdesivir is effective in the treatment of severe COVID-19 patients, in particular those without invasive ventilation
背景:2019年冠状病毒病(COVID-19)是由SARS-CoV-2感染引起的大流行疾病。已有5300多万人感染,130多万人死亡。然而,目前还没有标准的治疗方法或疫苗。最近,几项随机对照试验和队列研究证明了瑞德西韦治疗COVID-19重症患者的有效性。这是一项系统的综述和荟萃分析,以确定其疗效。方法:于2020年11月9日对PubMed、Embase、Medline、Cochrane等数据库进行系统评价。搜索关键词为瑞德西韦、COVID-19、SARS-CoV-2、随机对照试验和队列研究。选择具有高证据价值的研究,从风险比、临床改善时间和死亡风险等方面评价其临床疗效。根据基线住院状况、年龄和种族进行亚组分析。结果:在1328项研究中,选择6项研究进行荟萃分析。瑞德西韦与临床改善相关(风险比1.14,95% CI 1.02-1.28, p=0.02)。使临床改善时间缩短3.32天(95% CI -4.37 ~ -2.28, p<0.001)。然而,它的使用与降低死亡风险无关(风险比0.75,95% CI 0.40-1.40)。在亚组分析中,瑞德西韦与无需有创通气患者的临床改善相关(风险比1.90,95% CI 1.58-2.29, p<0.001;风险比2.22,95% CI, 1.64-3.02),年龄小于70岁(风险比2.14,95% CI 1.39-3.28, p<0.001)。结论:瑞德西韦治疗COVID-19重症患者疗效显著,尤其是无创通气患者
{"title":"Remdesivir for the Treatment of Severe SARS-CoV-2 (COVID-19): A Systematic Review and Meta-Analysis","authors":"Zhipeng Yan, K. Cheung, Eric Ho-Yin Lau, Ching‐lung Lai","doi":"10.31487/j.rgm.2020.04.01","DOIUrl":"https://doi.org/10.31487/j.rgm.2020.04.01","url":null,"abstract":"Background: Coronavirus Disease in 2019 (COVID-19) is a pandemic caused by SARS-CoV-2 infection.\u0000Over 53 million people have been infected with over 1.3 million deaths. However, there is no standard\u0000treatment or vaccines to date. Recently, several randomized controlled trials and cohort studies have\u0000demonstrated the efficacy of remdesivir for the treatment of severe COVID-19 patients. This is a systematic\u0000review and meta-analysis to define its efficacy.\u0000Methods: A systematic review was done on databases (PubMed, Embase, Medline, Cochrane) on 9 Nov\u00002020. Search keywords were remdesivir, COVID-19, SARS-CoV-2, randomized controlled trials and cohort\u0000studies. Studies with high-evidence values were selected to evaluate its clinical efficacy in terms of risk\u0000ratio, time to clinical improvement, and mortality risk. Subgroup analysis was performed based on baseline\u0000hospitalization status, age and ethnicity.\u0000Results: Of the 1328 studies, 6 studies were selected and pooled for meta-analysis. Remdesivir was\u0000associated with clinical improvement (risk ratio 1.14, 95% CI 1.02-1.28, p=0.02). It shortened the mean\u0000time of clinical improvement by 3.32 days (95% CI -4.37 to -2.28, p<0.001). However, its use was not\u0000associated with reduced mortality risk (risk ratio 0.75, 95% CI 0.40–1.40). In subgroup analysis, remdesivir\u0000was associated with clinical improvement in patients without the need of invasive ventilation (risk ratio\u00001.90, 95% CI 1.58-2.29, p<0.001; hazard ratio 2.22, 95% CI, 1.64-3.02), and age less than 70 years (risk\u0000ratio 2.14, 95% CI 1.39-3.28, p<0.001).\u0000Conclusion: Remdesivir is effective in the treatment of severe COVID-19 patients, in particular those\u0000without invasive ventilation","PeriodicalId":148803,"journal":{"name":"International Journal of Regenerative Medicine","volume":"98 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122486299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-06-18DOI: 10.31487/j.rgm.2020.02.01
M. Wheeler, Aaron J. Maki, A. C. M. Ercolin, J. J. Cooper, K. Roballo, M. Rubessa, R. Rabel
The primary aim of this study was to assess the therapeutic effects of autologous platelet-rich plasma and fibrin scaffolds combined with autologous adipose stem cells (ASCs) for critical-size defects in the pig mandible. Fibrin scaffolds supplemented with calcium hydrogen phosphate and platelet-derived growth factors were hypothesized to accelerate healing in porcine mandible bone compared to ASC-only injections and untreated controls. Three treatments included the use of autologous ASCs from liposuction with the addition of platelet-rich plasma, fibrin scaffolds, or as cell-only controls. All three treatments using ASCs were determined to increase bone mineral density and bone volume fraction compared to untreated controls. In general, the addition of both platelet-rich plasma and fibrin scaffolds to autologous ASCs from liposuction improved bone healing of critical-size defects.
{"title":"Autologous Adipose-Derived Stem Cells, Platelet-Rich Plasma, and Fibrin Enhance Healing of Mandibular Bone Defects in Swine","authors":"M. Wheeler, Aaron J. Maki, A. C. M. Ercolin, J. J. Cooper, K. Roballo, M. Rubessa, R. Rabel","doi":"10.31487/j.rgm.2020.02.01","DOIUrl":"https://doi.org/10.31487/j.rgm.2020.02.01","url":null,"abstract":"The primary aim of this study was to assess the therapeutic effects of autologous platelet-rich plasma and\u0000fibrin scaffolds combined with autologous adipose stem cells (ASCs) for critical-size defects in the pig\u0000mandible. Fibrin scaffolds supplemented with calcium hydrogen phosphate and platelet-derived growth\u0000factors were hypothesized to accelerate healing in porcine mandible bone compared to ASC-only injections\u0000and untreated controls. Three treatments included the use of autologous ASCs from liposuction with the\u0000addition of platelet-rich plasma, fibrin scaffolds, or as cell-only controls. All three treatments using ASCs\u0000were determined to increase bone mineral density and bone volume fraction compared to untreated controls.\u0000In general, the addition of both platelet-rich plasma and fibrin scaffolds to autologous ASCs from\u0000liposuction improved bone healing of critical-size defects.","PeriodicalId":148803,"journal":{"name":"International Journal of Regenerative Medicine","volume":"37 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116441546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-05-08DOI: 10.31487/j.rgm.2020.01.05
I. Triantafyllopoulos, N. Dede
Objective: We hypothesized that anabolic steroid administration would act synergistically with substrate strain in two-dimensional cultures of human supraspinatus tendon cells, to upregulate the expression of connexin-43 and to increase the Ca2+ wave propagation through gap junctions. Methods: Supraspinatus tendon cells were isolated intra-operatively from human specimens during shoulder arthroscopy. Cells were plated in two-dimensional spot cultures and arranged into four experimental groups: 1) non-load, non-steroid (NLNS, n=12 wells); 2) non-load, steroid (NLS, n=12 wells); 3) load, non-steroid (LNS, n=12 wells); and 4) load, steroid (LS, n=12 wells) in order to produce bioartificial tendons (BATs). The load groups were stretched in culture plates and the steroid groups were given nandrolone decanoate. When BATs were macro- and microscopically mature, at five days, they were evaluated with immunocytochemistry for connexin-43 staining, fluorescence microscopy for calcium imaging and mechanical stimulation with a micropipette tip manipulation for calcium propagation. Dose response test was performed in order to establish any relation between nandrolone decanoate dose and calcium signaling response. ATP was applied to the spot culture cells from all groups and all patients to determine if the cells were sensitive to extracellular ATP. Results: Load-steroid group demonstrated the greatest density of cnx43 in comparison to all other groups. There were no significant differences between the groups considering the percentage of cells responding after mechanical stimulation (cell recruitment). The cells of load-steroid group showed a significantly greater mean peak [Ca2+]ic compared to the values of the other groups (p<0.05). The propagation time was significantly decreased in the LS group compared with the other groups (p<0.05). There were no significant differences between the groups considering the number of cells that were responding spontaneously prior to stimulation or the number of responding cells that were oscillating after the stimulation. Conclusion: Nandrolone decanoate and loading seem to have a synergistic effect on the upregulation of the gap junction protein cxn43 enhancing calcium signaling via gap junctions. Consecutively, anabolic steroid administration and load may enhance the formation of a better-organized cytoskeleton and particularly the actin stress monofilaments.
{"title":"The Synergistic Effect of Anabolic Steroid and Loading on Intercellular Calcium Signaling Via Gap Junctions in Human Supraspinatus Tendon Cells","authors":"I. Triantafyllopoulos, N. Dede","doi":"10.31487/j.rgm.2020.01.05","DOIUrl":"https://doi.org/10.31487/j.rgm.2020.01.05","url":null,"abstract":"Objective: We hypothesized that anabolic steroid administration would act synergistically with substrate\u0000strain in two-dimensional cultures of human supraspinatus tendon cells, to upregulate the expression of\u0000connexin-43 and to increase the Ca2+ wave propagation through gap junctions.\u0000Methods: Supraspinatus tendon cells were isolated intra-operatively from human specimens during\u0000shoulder arthroscopy. Cells were plated in two-dimensional spot cultures and arranged into four\u0000experimental groups: 1) non-load, non-steroid (NLNS, n=12 wells); 2) non-load, steroid (NLS, n=12 wells);\u00003) load, non-steroid (LNS, n=12 wells); and 4) load, steroid (LS, n=12 wells) in order to produce bioartificial\u0000tendons (BATs). The load groups were stretched in culture plates and the steroid groups were given\u0000nandrolone decanoate. When BATs were macro- and microscopically mature, at five days, they were\u0000evaluated with immunocytochemistry for connexin-43 staining, fluorescence microscopy for calcium\u0000imaging and mechanical stimulation with a micropipette tip manipulation for calcium propagation. Dose\u0000response test was performed in order to establish any relation between nandrolone decanoate dose and\u0000calcium signaling response. ATP was applied to the spot culture cells from all groups and all patients to\u0000determine if the cells were sensitive to extracellular ATP.\u0000Results: Load-steroid group demonstrated the greatest density of cnx43 in comparison to all other groups.\u0000There were no significant differences between the groups considering the percentage of cells responding\u0000after mechanical stimulation (cell recruitment). The cells of load-steroid group showed a significantly\u0000greater mean peak [Ca2+]ic compared to the values of the other groups (p<0.05). The propagation time was\u0000significantly decreased in the LS group compared with the other groups (p<0.05). There were no significant\u0000differences between the groups considering the number of cells that were responding spontaneously prior\u0000to stimulation or the number of responding cells that were oscillating after the stimulation.\u0000Conclusion: Nandrolone decanoate and loading seem to have a synergistic effect on the upregulation of the\u0000gap junction protein cxn43 enhancing calcium signaling via gap junctions. Consecutively, anabolic steroid\u0000administration and load may enhance the formation of a better-organized cytoskeleton and particularly the\u0000actin stress monofilaments.","PeriodicalId":148803,"journal":{"name":"International Journal of Regenerative Medicine","volume":"40 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128924260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}