Pub Date : 2024-06-01DOI: 10.1016/j.reth.2024.06.015
Sainan Wang , Sicong Mao , Guibin Huang , Peipei Jia , Yanmei Dong , Jinxuan Zheng
Introduction
Dentin matrix extracted protein (DMEP) is a mixture of proteins extracted from the organic matrix of a natural demineralized dentin matrix that is rich in a variety of growth factors. However, the effect of DMEP on cartilage regeneration is unclear. The aim of this study was to investigate the efficacy of DMEP extracted via a novel alkali conditioning method in promoting cartilage regeneration.
Methods
Alkali-extracted DMEP (a-DMEP) was obtained from human dentin fragments using pH 10 bicarbonate buffer. The concentration of chondrogenesis-related growth factors in a-DMEP was measured via enzyme-linked immunosorbent assay (ELISA). Human bone marrow mesenchymal stem cells (hBMMSCs) in pellet form were induced with a-DMEP. Alcian blue and Safranin O staining were performed to detect cartilage matrix formation, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess chondrogenic-related gene expression in the pellets. Rabbit articular osteochondral defects were implanted with collagen and a-DMEP. Cartilage regeneration was assessed with histological staining 4 weeks after surgery.
Results
Compared with traditional neutral-extracted DMEP, a-DMEP significantly increased the levels of transforming growth factor beta 1(TGF-β1), insulin-like growth factor-1(IGF-1) and basic fibroblast growth factor (bFGF). After coculture with hBMMSC pellets, a-DMEP significantly promoted the expression of the collagen type II alpha 1(COL2A1) and aggrecan (ACAN) genes and the formation of cartilage extracellular matrix in cell pellets. Moreover, compared with equivalent amounts of exogenous human recombinant TGF-β1, a-DMEP had a stronger chondrogenic ability. In vivo, a-DMEP induced osteochondral regeneration with hyaline cartilage-like structures.
Conclusions
Our results showed that a-DMEP, a compound of various proteins derived from natural tissues, is a promising material for cartilage repair and regeneration.
{"title":"Alkali-extracted proteins from the tooth dentin matrix as a mixture of bioactive molecules for cartilage repair and regeneration","authors":"Sainan Wang , Sicong Mao , Guibin Huang , Peipei Jia , Yanmei Dong , Jinxuan Zheng","doi":"10.1016/j.reth.2024.06.015","DOIUrl":"https://doi.org/10.1016/j.reth.2024.06.015","url":null,"abstract":"<div><h3>Introduction</h3><p>Dentin matrix extracted protein (DMEP) is a mixture of proteins extracted from the organic matrix of a natural demineralized dentin matrix that is rich in a variety of growth factors. However, the effect of DMEP on cartilage regeneration is unclear. The aim of this study was to investigate the efficacy of DMEP extracted via a novel alkali conditioning method in promoting cartilage regeneration.</p></div><div><h3>Methods</h3><p>Alkali-extracted DMEP (a-DMEP) was obtained from human dentin fragments using pH 10 bicarbonate buffer. The concentration of chondrogenesis-related growth factors in a-DMEP was measured via enzyme-linked immunosorbent assay (ELISA). Human bone marrow mesenchymal stem cells (hBMMSCs) in pellet form were induced with a-DMEP. Alcian blue and Safranin O staining were performed to detect cartilage matrix formation, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess chondrogenic-related gene expression in the pellets. Rabbit articular osteochondral defects were implanted with collagen and a-DMEP. Cartilage regeneration was assessed with histological staining 4 weeks after surgery.</p></div><div><h3>Results</h3><p>Compared with traditional neutral-extracted DMEP, a-DMEP significantly increased the levels of transforming growth factor beta 1(TGF-β1), insulin-like growth factor-1(IGF-1) and basic fibroblast growth factor (bFGF). After coculture with hBMMSC pellets, a-DMEP significantly promoted the expression of the collagen type II alpha 1(COL2A1) and aggrecan (ACAN) genes and the formation of cartilage extracellular matrix in cell pellets. Moreover, compared with equivalent amounts of exogenous human recombinant TGF-β1, a-DMEP had a stronger chondrogenic ability. <em>In vivo,</em> a-DMEP induced osteochondral regeneration with hyaline cartilage-like structures.</p></div><div><h3>Conclusions</h3><p>Our results showed that a-DMEP, a compound of various proteins derived from natural tissues, is a promising material for cartilage repair and regeneration.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 407-414"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001226/pdfft?md5=2d5697cb4ee09d37d3a3a6bc458b63a1&pid=1-s2.0-S2352320424001226-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141540201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Repairing damaged cartilage poses significant challenges, particularly in cases of congenital cartilage defects such as microtia or congenital tracheal stenosis, or as a consequence of traumatic injury, as the regenerative potential of cartilage is inherently limited. Stem cell therapy and tissue engineering offer promising approaches to overcome these limitations in cartilage healing. However, the challenge lies in the size of cartilage-containing organs, which necessitates a large quantity of cells to fill the damaged areas. Therefore, pluripotent stem cells that can proliferate indefinitely are highly desirable as a cell source. This study aims to delineate the differentiation conditions for cartilage derived from human embryonic stem cells (ESCs) and to develop an automated cell culture system to facilitate mass production for therapeutic applications.
Methods
Cartilage cell sheets were derived from human ESCs (SEES2, clinical trial-compatible line) by forming embryoid bodies (EBs) with either conventional manual culture or a benchtop multi-pipetter and an automated medium exchange integrated cell incubator, using xeno-free media. Cell sheets were implanted into the subcutaneous tissue of immunodeficient NOG mice to obtain cartilage tissue. The properties of cartilage tissues were examined by histological staining and quantitative PCR analysis.
Results
We have optimized an efficient xeno-free system for cartilage production with the conventional culture method and successfully transitioned to an automated system. Differentiated cartilage was histologically uniform with cartilage-specific elasticity and strength. The cartilage tissues were stained by Alcian blue, safranin O, and toluidine blue, and quantitative PCR showed an increase in differentiation markers such as ACAN, COL2A1, and Vimentin. Automation significantly enhanced the efficiency of human ESC-derived chondrocyte differentiation. The number of constituent cells within EBs and the seeding density of EBs were identified as key factors influencing chondrogenic differentiation efficiency. By automating the process of chondrogenic differentiation, we achieved scalable production of chondrocytes.
Conclusions
By integrating the differentiation protocol with an automated cell culture system, there is potential to produce cartilage of sufficient size for clinical applications in humans. The resulting cartilage tissue holds promise for clinical use in repairing organs such as the trachea, joints, ears, and nose.
导言:修复受损软骨是一项重大挑战,尤其是在先天性软骨缺损(如小耳症或先天性气管狭窄)或外伤的情况下,因为软骨的再生潜力本身就是有限的。干细胞疗法和组织工程学为克服软骨愈合中的这些局限性提供了前景广阔的方法。然而,挑战在于含软骨器官的大小,这就需要大量细胞来填充受损区域。因此,可无限增殖的多能干细胞是非常理想的细胞来源。本研究旨在确定从人类胚胎干细胞(ESCs)中提取软骨的分化条件,并开发一种自动化细胞培养系统,以促进治疗应用的大规模生产。方法通过传统的手工培养或台式多管培养器和自动培养基交换集成细胞培养箱,使用无异种培养基形成胚状体(EBs),从人类ESCs(SEES2,临床试验兼容品系)中提取软骨细胞片。将细胞片植入免疫缺陷 NOG 小鼠的皮下组织以获得软骨组织。通过组织学染色和定量 PCR 分析检测了软骨组织的特性。分化的软骨在组织学上是一致的,具有软骨特有的弹性和强度。软骨组织经阿尔新蓝、黄芩苷 O 和甲苯胺蓝染色,定量 PCR 显示 ACAN、COL2A1 和 Vimentin 等分化标记物增加。自动化大大提高了人ESC衍生软骨细胞分化的效率。EB 中组成细胞的数量和 EB 的播种密度是影响软骨分化效率的关键因素。通过将软骨分化过程自动化,我们实现了软骨细胞的规模化生产。由此产生的软骨组织有望用于气管、关节、耳朵和鼻子等器官的临床修复。
{"title":"Automated xeno-free chondrogenic differentiation from human embryonic stem cells: Enhancing efficiency and ensuring high-quality mass production","authors":"JunLong Chen , Oki Kataoka , Kazeto Tsuchiya , Yoshie Oishi , Ayumi Takao , Yen-Chih Huang , Hiroko Komura , Saeko Akiyama , Ren Itou , Masafumi Inui , Shin Enosawa , Hidenori Akutsu , Makoto Komura , Yasushi Fuchimoto , Akihiro Umezawa","doi":"10.1016/j.reth.2024.09.007","DOIUrl":"10.1016/j.reth.2024.09.007","url":null,"abstract":"<div><h3>Introduction</h3><div>Repairing damaged cartilage poses significant challenges, particularly in cases of congenital cartilage defects such as microtia or congenital tracheal stenosis, or as a consequence of traumatic injury, as the regenerative potential of cartilage is inherently limited. Stem cell therapy and tissue engineering offer promising approaches to overcome these limitations in cartilage healing. However, the challenge lies in the size of cartilage-containing organs, which necessitates a large quantity of cells to fill the damaged areas. Therefore, pluripotent stem cells that can proliferate indefinitely are highly desirable as a cell source. This study aims to delineate the differentiation conditions for cartilage derived from human embryonic stem cells (ESCs) and to develop an automated cell culture system to facilitate mass production for therapeutic applications.</div></div><div><h3>Methods</h3><div>Cartilage cell sheets were derived from human ESCs (SEES2, clinical trial-compatible line) by forming embryoid bodies (EBs) with either conventional manual culture or a benchtop multi-pipetter and an automated medium exchange integrated cell incubator, using xeno-free media. Cell sheets were implanted into the subcutaneous tissue of immunodeficient NOG mice to obtain cartilage tissue. The properties of cartilage tissues were examined by histological staining and quantitative PCR analysis.</div></div><div><h3>Results</h3><div>We have optimized an efficient xeno-free system for cartilage production with the conventional culture method and successfully transitioned to an automated system. Differentiated cartilage was histologically uniform with cartilage-specific elasticity and strength. The cartilage tissues were stained by Alcian blue, safranin O, and toluidine blue, and quantitative PCR showed an increase in differentiation markers such as ACAN, COL2A1, and Vimentin. Automation significantly enhanced the efficiency of human ESC-derived chondrocyte differentiation. The number of constituent cells within EBs and the seeding density of EBs were identified as key factors influencing chondrogenic differentiation efficiency. By automating the process of chondrogenic differentiation, we achieved scalable production of chondrocytes.</div></div><div><h3>Conclusions</h3><div>By integrating the differentiation protocol with an automated cell culture system, there is potential to produce cartilage of sufficient size for clinical applications in humans. The resulting cartilage tissue holds promise for clinical use in repairing organs such as the trachea, joints, ears, and nose.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 889-900"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Because hair loss is a common concern for many individuals, potential regenerative therapies of hair follicles have been extensively researched. Induced pluripotent stem cells (iPSCs) are a promising avenue for hair follicle regeneration. This review explores current iPSC-based approaches and highlights their potential applications and challenges in hair restoration. The principles of iPSC technology, iPSC differentiation into hair follicle precursor cells, and potential clinical implications for hair follicle regeneration are also discussed. This overview of iPSCs and their applications aims to contribute to our understanding of their role in hair restoration and potential future therapeutic applications.
{"title":"An induced pluripotent stem cell-based approach for hair follicle development and regeneration","authors":"Poornima Sivamani , Ramya Lakshmi Rajendran , Prakash Gangadaran , Byeong-Cheol Ahn","doi":"10.1016/j.reth.2024.07.005","DOIUrl":"10.1016/j.reth.2024.07.005","url":null,"abstract":"<div><p>Because hair loss is a common concern for many individuals, potential regenerative therapies of hair follicles have been extensively researched. Induced pluripotent stem cells (iPSCs) are a promising avenue for hair follicle regeneration. This review explores current iPSC-based approaches and highlights their potential applications and challenges in hair restoration. The principles of iPSC technology, iPSC differentiation into hair follicle precursor cells, and potential clinical implications for hair follicle regeneration are also discussed. This overview of iPSCs and their applications aims to contribute to our understanding of their role in hair restoration and potential future therapeutic applications.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 502-507"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001330/pdfft?md5=aafe1999e011a3ca3b4257eba2e06a38&pid=1-s2.0-S2352320424001330-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141960696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.reth.2024.08.002
Juan Li, Hao Li, Kaikai Wang, Haiyan Chou
The management of burn injuries presents a significant challenge in clinical settings, yet an optimal solution remains elusive. Therefore, this study aimed to develop a topical therapeutic formulation to address the complex issues hindering burn wound healing. Emphasizing the sustained presence of bioactive principles, we synthesized a bioactive gel derived from decellularized caprine small intestine submucosa (D-CIS) and encapsulated it with nano-formulations of cerium oxide and curcumin to create a burn wound dressing material with enhanced properties. The choice of encapsulated components was guided by their antimicrobial, antioxidant, and immune-modulating characteristics, along with their inherent ability to gradually release bioactive substances. The encapsulated (cerium oxide and curcumin) D-CIS bioactive gel demonstrated a range of properties, including antimicrobial, antioxidant, and anti-inflammatory effects, along with sustained release kinetics of bioactive molecules. These combined effects facilitated accelerated burn wound healing by mitigating oxidative stress, reducing inflammation, and promoting cell recruitment for epithelial and vascular regeneration. This study contributes to the development of a novel bioactive gel incorporating cerium oxide and curcumin, offering a promising approach to enhance burn wound healing.
{"title":"Evaluation of decellularized caprine small intestine submucosa encapsulated with nano-formulations of cerium oxide and curcumin in the management of burn wound","authors":"Juan Li, Hao Li, Kaikai Wang, Haiyan Chou","doi":"10.1016/j.reth.2024.08.002","DOIUrl":"10.1016/j.reth.2024.08.002","url":null,"abstract":"<div><p>The management of burn injuries presents a significant challenge in clinical settings, yet an optimal solution remains elusive. Therefore, this study aimed to develop a topical therapeutic formulation to address the complex issues hindering burn wound healing. Emphasizing the sustained presence of bioactive principles, we synthesized a bioactive gel derived from decellularized caprine small intestine submucosa (D-CIS) and encapsulated it with nano-formulations of cerium oxide and curcumin to create a burn wound dressing material with enhanced properties. The choice of encapsulated components was guided by their antimicrobial, antioxidant, and immune-modulating characteristics, along with their inherent ability to gradually release bioactive substances. The encapsulated (cerium oxide and curcumin) D-CIS bioactive gel demonstrated a range of properties, including antimicrobial, antioxidant, and anti-inflammatory effects, along with sustained release kinetics of bioactive molecules. These combined effects facilitated accelerated burn wound healing by mitigating oxidative stress, reducing inflammation, and promoting cell recruitment for epithelial and vascular regeneration. This study contributes to the development of a novel bioactive gel incorporating cerium oxide and curcumin, offering a promising approach to enhance burn wound healing.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 578-589"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S235232042400138X/pdfft?md5=0657916ddadec7031d61b2df7f6a42e4&pid=1-s2.0-S235232042400138X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141985394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.reth.2024.04.014
Yujin Zhang , Qing Tang , Bijun Zeng , Fengjiao Wang , Meijunzi Luo , Pan Huang , Ling Chen , Haizhen Wang
Introduction
Hair loss is one of the common clinical conditions in modern society. Although it is not a serious disease that threatens human life, it brings great mental stress and psychological burden to patients. This study investigated the role of dendrobium officinale polysaccharide (DOP) in hair follicle regeneration and hair growth and its related mechanisms.
Methods
After in vitro culture of mouse antennal hair follicles and mouse dermal papilla cells (DPCs), and mouse vascular endothelial cells (MVECs), the effects of DOP upon hair follicles and cells were evaluated using multiple methods. DOP effects were evaluated by measuring tentacle growth, HE staining, immunofluorescence, Western blot, CCK-8, ALP staining, tube formation, scratch test, and Transwell. LDH levels, WNT signaling proteins, and therapeutic mechanisms were also analyzed.
Results
DOP promoted tentacle hair follicle and DPCs growth in mice and the angiogenic, migratory and invasive capacities of MVECs. Meanwhile, DOP was also capable of enhancing angiogenesis and proliferation-related protein expression. Mechanistically, DOP activated the WNT signaling and promoted the expression level of β-catenin, a pivotal protein of the pathway, and the pathway target proteins Cyclin D1, C-Myc, and LDH activity. The promotional effects of DOP on the biological functions of DPCs and MVECs could be effectively reversed by the WNT signaling pathway inhibitor IWR-1.
Conclusion
DOP advances hair follicle and hair growth via the activation of the WNT signaling. This finding provides a mechanistic reference and theoretical basis for the clinical use of DOP in treating hair loss.
{"title":"Dendrobium officinale polysaccharide promotes angiogenesis as well as follicle regeneration and hair growth through activation of the WNT signaling pathway","authors":"Yujin Zhang , Qing Tang , Bijun Zeng , Fengjiao Wang , Meijunzi Luo , Pan Huang , Ling Chen , Haizhen Wang","doi":"10.1016/j.reth.2024.04.014","DOIUrl":"10.1016/j.reth.2024.04.014","url":null,"abstract":"<div><h3>Introduction</h3><p>Hair loss is one of the common clinical conditions in modern society. Although it is not a serious disease that threatens human life, it brings great mental stress and psychological burden to patients. This study investigated the role of dendrobium officinale polysaccharide (DOP) in hair follicle regeneration and hair growth and its related mechanisms.</p></div><div><h3>Methods</h3><p>After in vitro culture of mouse antennal hair follicles and mouse dermal papilla cells (DPCs), and mouse vascular endothelial cells (MVECs), the effects of DOP upon hair follicles and cells were evaluated using multiple methods. DOP effects were evaluated by measuring tentacle growth, HE staining, immunofluorescence, Western blot, CCK-8, ALP staining, tube formation, scratch test, and Transwell. LDH levels, WNT signaling proteins, and therapeutic mechanisms were also analyzed.</p></div><div><h3>Results</h3><p>DOP promoted tentacle hair follicle and DPCs growth in mice and the angiogenic, migratory and invasive capacities of MVECs. Meanwhile, DOP was also capable of enhancing angiogenesis and proliferation-related protein expression. Mechanistically, DOP activated the WNT signaling and promoted the expression level of β-catenin, a pivotal protein of the pathway, and the pathway target proteins Cyclin D1, C-Myc, and LDH activity. The promotional effects of DOP on the biological functions of DPCs and MVECs could be effectively reversed by the WNT signaling pathway inhibitor IWR-1.</p></div><div><h3>Conclusion</h3><p>DOP advances hair follicle and hair growth via the activation of the WNT signaling. This finding provides a mechanistic reference and theoretical basis for the clinical use of DOP in treating hair loss.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 114-123"},"PeriodicalIF":4.3,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424000762/pdfft?md5=796b2901d043d3886dbd25543de6343c&pid=1-s2.0-S2352320424000762-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141231334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.reth.2024.02.006
Masoumeh Einabadi , Azadeh Izadyari Aghmiuni , Laleh Foroutani , Arman Ai , Mojdeh Salehi Namini , Ali Farzin , Amir Nahanmoghadam , Sadegh Shirian , Hossein Kargar Jahromi , Jafar Ai
This study aimed to evaluate the effect of nanoparticles based on the PLGA and biomolecule of lycopene (i.e. NLcp) and exosomes loaded on hydroxyapatite/collagen-based scaffolds (HA/Coll), on human endometrial MSCs (hEnMSCs) differentiation into osteoblast cells. To this end, after synthesizing NLcp and isolating hEnMSC-derived exosomes, and studying their characterizations, HA/Coll scaffold with/without NLcp and exosome was fabricated. In following, the rat skull-defect model was created on 54 male Sprague–Dawley rats (12 weeks old) which were classified into 6 groups [control group (4 healthy rats), negative control group: bone defect without grafting (10 rats), and experimental groups including bone defect grafted with HA/Coll scaffold (10 rats), HA/Coll/NLcp scaffold (10 rats), HA/Coll scaffold + exosome (10 rats), and HA/Coll-NLcp scaffold + exosome (10 rats)]. Finally, the grafted membrane along with its surrounding tissues was removed at 90 days after surgery, to assess the amount of defect repair by Hematoxylin and eosin staining. Moreover, immunohistochemical and X-ray Micro-Computed Tomography (Micro-CT) analyses were performed to assess osteocalcin and mean bone volume fraction (BVF). Based on the results, although, the existence of the exosome in the scaffold network can significantly increase mean BVF compared to HA/Coll scaffold and HA/Coll-NLcp scaffold (2.25-fold and 1.5-fold, respectively). However, the combination of NLcp and exosome indicated more effect on mean BVF; so that the HA/Coll-NLcp scaffold + exosome led to a 15.95 % increase in mean BVF than the HA/Coll scaffold + exosome. Hence, synthesized NLcp in this study can act as a suitable bioactive to stimulate the osteogenic, promotion of cell proliferation and its differentiation when used in the polymer scaffold structure or loaded into polymeric carriers containing the exosome.
{"title":"Evaluation of the effect of co-transplantation of collagen-hydroxyapatite bio-scaffold containing nanolycopene and human endometrial mesenchymal stem cell derived exosomes to regenerate bone in rat critical size calvarial defect","authors":"Masoumeh Einabadi , Azadeh Izadyari Aghmiuni , Laleh Foroutani , Arman Ai , Mojdeh Salehi Namini , Ali Farzin , Amir Nahanmoghadam , Sadegh Shirian , Hossein Kargar Jahromi , Jafar Ai","doi":"10.1016/j.reth.2024.02.006","DOIUrl":"https://doi.org/10.1016/j.reth.2024.02.006","url":null,"abstract":"<div><p>This study aimed to evaluate the effect of nanoparticles based on the PLGA and biomolecule of lycopene (i.e. NLcp) and exosomes loaded on hydroxyapatite/collagen-based scaffolds (HA/Coll), on human endometrial MSCs (hEnMSCs) differentiation into osteoblast cells. To this end, after synthesizing NLcp and isolating hEnMSC-derived exosomes, and studying their characterizations, HA/Coll scaffold with/without NLcp and exosome was fabricated. In following, the rat skull-defect model was created on 54 male Sprague–Dawley rats (12 weeks old) which were classified into 6 groups [control group (4 healthy rats), negative control group: bone defect without grafting (10 rats), and experimental groups including bone defect grafted with HA/Coll scaffold (10 rats), HA/Coll/NLcp scaffold (10 rats), HA/Coll scaffold + exosome (10 rats), and HA/Coll-NLcp scaffold + exosome (10 rats)]. Finally, the grafted membrane along with its surrounding tissues was removed at 90 days after surgery, to assess the amount of defect repair by Hematoxylin and eosin staining. Moreover, immunohistochemical and X-ray Micro-Computed Tomography (Micro-CT) analyses were performed to assess osteocalcin and mean bone volume fraction (BVF). Based on the results, although, the existence of the exosome in the scaffold network can significantly increase mean BVF compared to HA/Coll scaffold and HA/Coll-NLcp scaffold (2.25-fold and 1.5-fold, respectively). However, the combination of NLcp and exosome indicated more effect on mean BVF; so that the HA/Coll-NLcp scaffold + exosome led to a 15.95 % increase in mean BVF than the HA/Coll scaffold + exosome. Hence, synthesized NLcp in this study can act as a suitable bioactive to stimulate the osteogenic, promotion of cell proliferation and its differentiation when used in the polymer scaffold structure or loaded into polymeric carriers containing the exosome.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 387-400"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424000208/pdfft?md5=97a6108947b623e514236228a5f71803&pid=1-s2.0-S2352320424000208-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141484342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This present study evaluated the effect of combination therapy with stromal cell-derived factor 1α (SDF-1α) and high-mobility group box 1 (HMGB1) peptide on the regeneration of tracheal injury in a rat model.
Methods
To improve this effect, SDF-1α was incorporated into a gelatin hydrogel, which was then applied to the damaged tracheal cartilage of rats for local release. Furthermore, HMGB1 peptide was repeatedly administered intravenously. Regeneration of damaged tracheal cartilage was evaluated in terms of cell recruitment.
Results
Mesenchymal stem cells (MSC) with C-X-C motif chemokine receptor 4 (CXCR4) were mobilized more into the injured area, and consequently the fastest tracheal cartilage regeneration was observed in the combination therapy group eight weeks after injury.
Conclusions
The present study demonstrated that combination therapy with gelatin hydrogel incorporating SDF-1α and HMGB1 peptide injected intravenously can enhance the recruitment of CXCR4-positive MSC, promoting the regeneration of damaged tracheal cartilage.
{"title":"Enhancement of tracheal cartilage regeneration by local controlled release of stromal cell-derived factor 1α with gelatin hydrogels and systemic administration of high-mobility group box 1 peptide","authors":"Kumiko (Ogi) Suzuki , Tatsuya Okamoto , Katsuto Tamai , Yasuhiko Tabata , Etsuro Hatano","doi":"10.1016/j.reth.2024.06.017","DOIUrl":"https://doi.org/10.1016/j.reth.2024.06.017","url":null,"abstract":"<div><h3>Introduction</h3><p>This present study evaluated the effect of combination therapy with stromal cell-derived factor 1α (SDF-1α) and high-mobility group box 1 (HMGB1) peptide on the regeneration of tracheal injury in a rat model.</p></div><div><h3>Methods</h3><p>To improve this effect, SDF-1α was incorporated into a gelatin hydrogel, which was then applied to the damaged tracheal cartilage of rats for local release. Furthermore, HMGB1 peptide was repeatedly administered intravenously. Regeneration of damaged tracheal cartilage was evaluated in terms of cell recruitment.</p></div><div><h3>Results</h3><p>Mesenchymal stem cells (MSC) with C-X-C motif chemokine receptor 4 (CXCR4) were mobilized more into the injured area, and consequently the fastest tracheal cartilage regeneration was observed in the combination therapy group eight weeks after injury.</p></div><div><h3>Conclusions</h3><p>The present study demonstrated that combination therapy with gelatin hydrogel incorporating SDF-1α and HMGB1 peptide injected intravenously can enhance the recruitment of CXCR4-positive MSC, promoting the regeneration of damaged tracheal cartilage.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 415-424"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S235232042400124X/pdfft?md5=5b5e3bec8f2ef765b84a2e6215373d99&pid=1-s2.0-S235232042400124X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141540151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Osseointegration, the direct contact between an implant and bone, can be achieved by direct and/or indirect osteogenesis. Platelet-rich plasma accelerates tissue regeneration, wound healing, and osseointegration. This study aimed to analyze the effects of leukocyte and platelet-rich plasma (L-PRP) on direct and indirect osteogenesis after implant placement in a mouse maxilla.
Methods
Blood was collected from the tail vein of 4–8-week-old male ICR mice and L-PRP was obtained after double-spin cycle centrifugation. After the right upper first molars of 4-week-old ICR mice were extracted while under deep anesthesia, the alveolar sockets were prepared with a drill, and titanium implants blasted with hydroxyapatite/β-tricalcium phosphate were placed into the cavity filled with 1.5 μL of L-PRP. Samples were collected from the animals 3–28 days after implantation, and immunohistochemistry for osteopontin, Ki67 (cell proliferation marker), cathepsin-K (osteoclast marker), and osteonectin (osteoblast marker) was performed.
Results
Cell proliferation was significantly higher in the L-PRP group than in the control group on postoperative days 3 and 5. The activities of osteoclast-lineage cells and osteoblasts increased significantly on day 5 in the L-PRP group, indicating that L-PRP evoked an active cellular response. Indirect osteogenesis was significantly higher on days 7, 14, and 28, and the osseointegration rate was significantly higher on day 28 in the L-PRP group compared with the control group.
Conclusions
L-PRP enhances osseointegration by promoting mesenchymal cell proliferation, osteoclastic and osteoblastic activities, and indirect osteogenesis.
{"title":"Effect of leukocyte and platelet-rich plasma on osseointegration after implant placement in mouse maxilla","authors":"Mauricio Zapata-Sifuentes , Angela Quispe-Salcedo , Taisuke Watanabe , Tomoyuki Kawase , Hayato Ohshima","doi":"10.1016/j.reth.2024.08.019","DOIUrl":"10.1016/j.reth.2024.08.019","url":null,"abstract":"<div><h3>Introduction</h3><p>Osseointegration, the direct contact between an implant and bone, can be achieved by direct and/or indirect osteogenesis. Platelet-rich plasma accelerates tissue regeneration, wound healing, and osseointegration. This study aimed to analyze the effects of leukocyte and platelet-rich plasma (L-PRP) on direct and indirect osteogenesis after implant placement in a mouse maxilla.</p></div><div><h3>Methods</h3><p>Blood was collected from the tail vein of 4–8-week-old male ICR mice and L-PRP was obtained after double-spin cycle centrifugation. After the right upper first molars of 4-week-old ICR mice were extracted while under deep anesthesia, the alveolar sockets were prepared with a drill, and titanium implants blasted with hydroxyapatite/β-tricalcium phosphate were placed into the cavity filled with 1.5 μL of L-PRP. Samples were collected from the animals 3–28 days after implantation, and immunohistochemistry for osteopontin, Ki67 (cell proliferation marker), cathepsin-K (osteoclast marker), and osteonectin (osteoblast marker) was performed.</p></div><div><h3>Results</h3><p>Cell proliferation was significantly higher in the L-PRP group than in the control group on postoperative days 3 and 5. The activities of osteoclast-lineage cells and osteoblasts increased significantly on day 5 in the L-PRP group, indicating that L-PRP evoked an active cellular response. Indirect osteogenesis was significantly higher on days 7, 14, and 28, and the osseointegration rate was significantly higher on day 28 in the L-PRP group compared with the control group.</p></div><div><h3>Conclusions</h3><p>L-PRP enhances osseointegration by promoting mesenchymal cell proliferation, osteoclastic and osteoblastic activities, and indirect osteogenesis.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 741-748"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S235232042400155X/pdfft?md5=86bec1fba8621e6d3605d75d575bffcc&pid=1-s2.0-S235232042400155X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142151839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Calcium oscillations are rhythmic fluctuations of the intracellular concentration of calcium ions (Ca2+). As Ca2+ evokes various cellular processes, its intracellular concentration is tightly regulated. Ca2+ oscillations control biological events, including neuronal differentiation and proliferation of mesenchymal stem cells. The frequency and pattern of Ca2+ oscillations depend on cell type. Researchers have studied Ca2+ oscillations to better understand how cells communicate and regulate physiological processes. Dysregulation of Ca2+ oscillations causes health problems, such as neurodegenerative disorders. This review discusses the potential functions of Ca2+ oscillations in stem cells.
{"title":"Calcium oscillations and mitochondrial enzymes in stem cells","authors":"Mio Fukuoka , Woojin Kang , Sae Horiike , Mitsutoshi Yamada , Kenji Miyado","doi":"10.1016/j.reth.2024.09.002","DOIUrl":"10.1016/j.reth.2024.09.002","url":null,"abstract":"<div><p>Calcium oscillations are rhythmic fluctuations of the intracellular concentration of calcium ions (Ca<sup>2+</sup>). As Ca<sup>2+</sup> evokes various cellular processes, its intracellular concentration is tightly regulated. Ca<sup>2+</sup> oscillations control biological events, including neuronal differentiation and proliferation of mesenchymal stem cells. The frequency and pattern of Ca<sup>2+</sup> oscillations depend on cell type. Researchers have studied Ca<sup>2+</sup> oscillations to better understand how cells communicate and regulate physiological processes. Dysregulation of Ca<sup>2+</sup> oscillations causes health problems, such as neurodegenerative disorders. This review discusses the potential functions of Ca<sup>2+</sup> oscillations in stem cells.</p></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 811-818"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352320424001639/pdfft?md5=3fade2e99a200ef761478d7c67b4f899&pid=1-s2.0-S2352320424001639-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.reth.2024.10.008
Xun Xu , Jun Wang , Tian-Ci Sun , Qing Li , Ren-De Ning
Hydrogel has emerged as a promising wound dressing material, and in situ forming hydrogel has emerged as a promising wound dressing recently. But most in situ forming hydrogel are normally unstable. Herein, we report an in-situ forming hydrogel synthesized from poly(Nisopropylacrylamide166-co-n-butyl acrylate9)-poly(ethyleneglycol)-poly(N-isopropylacrylamide166-co-n-butyl acrylate9) copolymer (P(NIPAM166-co-nBA9)-PEG-P(NIPAM166-conBA9), denoted as PEP) and zinc oxide nano-particle(ZnO nano-particle) in response to skin temperature. This thermoresponsive hydrogel exhibits sol-gel reversibility at high temperatures, which is closed to the temperature of human skin. To investigate its healing effects, we used the Hydrogel dressing® in an SD rat model. The biocompatibility and antibacterial ability against methicillin-resistant Staphylococcus aureus(MRSA) of this PEP-ZnO hydrogel wound dressing are confirmed in vitro and in vivo, which could transparently promote the healing of a MRSA-infected frostbitten skin Injury.
Materials and methods
Thirty rats were randomly divided into two groups. The treatment group received hydrogel and transparent film dressing 30 min to 1 h post-burn, while the control group received only cotton dressing. The wound area was measured, and the wound closure rate was calculated on days 3, 7, and 14 post-surgery. Tissue samples were collected from each rat on these days and stored at −80 °C for histological analysis using H&E, Masson and immunohistochemical staining. This analysis assessed factors such as granulation tissue length, re-epithelialization, re-angiogenesis, collagen deposition, inflammatory cell infiltration, and collagen production. Clinical and histological assessments at 14 days showed more rapid healing in the hydrogel dressing group compared to the control group.
Conclusion
Our results indicate that the design of our hydrogel for cooling injury wounds effectively improves healing and mitigates the damage from low temperatures.
{"title":"In situ forming Hydrogel with adding ZnO Nano-particle for effectively methicillin-resistant Staphylococcus aureus infected frostbite injury","authors":"Xun Xu , Jun Wang , Tian-Ci Sun , Qing Li , Ren-De Ning","doi":"10.1016/j.reth.2024.10.008","DOIUrl":"10.1016/j.reth.2024.10.008","url":null,"abstract":"<div><div>Hydrogel has emerged as a promising wound dressing material, and in situ forming hydrogel has emerged as a promising wound dressing recently. But most in situ forming hydrogel are normally unstable. Herein, we report an in-situ forming hydrogel synthesized from poly(Nisopropylacrylamide166-<em>co</em>-<em>n</em>-butyl acrylate9)-poly(ethyleneglycol)-poly(N-isopropylacrylamide166-<em>co</em>-<em>n</em>-butyl acrylate9) copolymer (P(NIPAM166-<em>co</em>-nBA9)-PEG-P(NIPAM166-conBA9), denoted as PEP) and zinc oxide nano-particle(ZnO nano-particle) in response to skin temperature. This thermoresponsive hydrogel exhibits sol-gel reversibility at high temperatures, which is closed to the temperature of human skin. To investigate its healing effects, we used the Hydrogel dressing® in an SD rat model. The biocompatibility and antibacterial ability against methicillin-resistant Staphylococcus aureus(MRSA) of this PEP-ZnO hydrogel wound dressing are confirmed in vitro and in vivo, which could transparently promote the healing of a MRSA-infected frostbitten skin Injury.</div></div><div><h3>Materials and methods</h3><div>Thirty rats were randomly divided into two groups. The treatment group received hydrogel and transparent film dressing 30 min to 1 h post-burn, while the control group received only cotton dressing. The wound area was measured, and the wound closure rate was calculated on days 3, 7, and 14 post-surgery. Tissue samples were collected from each rat on these days and stored at −80 °C for histological analysis using H&E, Masson and immunohistochemical staining. This analysis assessed factors such as granulation tissue length, re-epithelialization, re-angiogenesis, collagen deposition, inflammatory cell infiltration, and collagen production. Clinical and histological assessments at 14 days showed more rapid healing in the hydrogel dressing group compared to the control group.</div></div><div><h3>Conclusion</h3><div>Our results indicate that the design of our hydrogel for cooling injury wounds effectively improves healing and mitigates the damage from low temperatures.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"Pages 956-966"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}