Regenerative Therapy最新文献_第5页

Establishment of feline embryonic stem cells from the inner cell mass of blastocysts produced in vitro 猫胚泡内细胞群体外培养胚胎干细胞的建立

IF 3.4 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2024-12-02 DOI: 10.1016/j.reth.2024.11.010

Takumi Yoshida , Masaya Tsukamoto , Kazuto Kimura , Miyuu Tanaka , Mitsuru Kuwamura , Shingo Hatoya

Introduction

The rising number of cats as pets and the growing interest in animal welfare have led to an increased need for the latest treatments in feline veterinary medicine. Among these, veterinary regenerative medicine using pluripotent stem cells is gaining significant attention. However, there have been no reports on establishing feline embryonic stem cell (ESC) lines that possess the pluripotent potential and the ability to differentiate into three germ layers.

Methods

In this study, we isolated three inner cell masses from feline in vitro-derived blastocysts and subcultured them in a chemically defined medium (StemFit AK02N). We assessed the expression of undifferentiated markers, the ability to differentiate into the three germ layers, and the karyotype structure.

Results

We established three feline ESC lines. Feline ESCs exhibited positive staining for alkaline phosphatase. RT-qPCR analysis revealed that these cells express undifferentiated marker genes in vitro. Immunostaining and flow cytometry analysis demonstrated that feline ESCs express undifferentiated marker proteins in vitro. In the KSR/FBS medium with or without Activin A, feline ESCs differentiated into all three germ layers (ectoderm, endoderm, and mesoderm), expressing specific marker genes and proteins for each germ layer, as evidenced by RT-qPCR, immunostaining, and flow cytometry. Furthermore, we confirmed that feline ESCs formed teratomas comprising all three germ layers in mouse testes, demonstrating de novo pluripotency in vivo. We also verified that the feline ESCs maintained a normal karyotype.

Conclusions

We successfully established three feline ESC lines, each possessing pluripotent potential and capable of differentiating into all three germ layers, derived from the inner cell masses of blastocysts produced in vitro.

越来越多的猫作为宠物和越来越多的人对动物福利的兴趣导致了对猫兽医最新治疗方法的需求增加。其中，利用多能干细胞的兽医再生医学正受到极大的关注。然而，目前还没有关于建立具有多能潜能和分化成三种胚层能力的猫胚胎干细胞（ESC）系的报道。方法在本研究中，我们从体外培养的猫囊胚中分离出3个内细胞团，并在化学定义的培养基（StemFit AK02N）中进行传代培养。我们评估了未分化标记的表达，向三个胚层分化的能力和核型结构。结果建立了3条猫ESC细胞系。猫ESCs呈碱性磷酸酶阳性染色。RT-qPCR分析显示，这些细胞在体外表达未分化的标记基因。免疫染色和流式细胞术分析表明，猫ESCs在体外表达未分化的标记蛋白。RT-qPCR、免疫染色和流式细胞术证实，在有或没有激活素A的KSR/FBS培养基中，猫ESCs分化为所有三个胚层（外胚层、内胚层和中胚层），表达每个胚层的特定标记基因和蛋白质。此外，我们证实了猫ESCs在小鼠睾丸中形成包含所有三种胚层的畸胎瘤，在体内表现出新生多能性。我们还验证了猫ESCs保持正常的核型。结论从体外培养的囊胚内细胞团中成功建立了3个具有多能性并能分化为所有3种胚层的猫ESC系。

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引用次数: 0

Establishment of a mouse organ culture model of fetal cleft lip for the evaluation of adipose-derived stem cell therapy 建立小鼠胎儿唇裂器官培养模型评价脂肪源性干细胞治疗效果

IF 3.4 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2024-11-30 DOI: 10.1016/j.reth.2024.11.012

Ayane Fukutome , Tomoaki Sakamoto , Yukiyo Asawa , Dan Riu , Hiroshi Kawakami , Kazuto Hoshi , Atsuhiko Hikita

Introduction

Cleft lip and cleft palate are congenital disorders resulting from abnormal facial development. Current treatments require multiple surgeries, which have risks of scar formation and facial deformities. Recently, fetal treatments utilizing “scarless healing” have gained attention, as early intervention shows potential to suppress scarring. In the field of regenerative medicine, mesenchymal stem cell therapies using cell sheets have advanced, by which promotion of tissue repair is expected. However, researches for fetal treatment using small animal models of cleft lip are challenging due to the high fetal mortality caused by surgical invasiveness. Although organ culture methods may offer an alternative approach, no organ culture system for fetal cleft lip research has been reported.

Methods

In this study, a cleft lip was surgically created on the upper left side lip of E15.5 mouse fetuses. These fetuses were cultured for four days using an organ culture system. Histological evaluation was performed to evaluate cell density, tissue morphology, and epithelialization. Additionally, adipose-derived stem cell (ADSC) sheets were transplanted two days after cleft lip creation to evaluate their effect on tissue repair.

Results

The histological analysis showed that cell density and tissue morphology were stably maintained in the four-day culture period. Epithelialization of the incision site was observed two days after surgery, confirming the completion of cleft formation. In the ADSC-transplanted group, epithelialization of the cleft site was observed, which indicates that the stem cell sheets contributed to tissue repair.

Conclusion

This research demonstrates the successful development of a cleft lip organ culture model and highlights the potential of ADSC sheets in promoting tissue repair. These findings provide a foundation for future regenerative medicine strategies in fetal cleft lip therapy.

唇腭裂是由面部发育异常引起的先天性疾病。目前的治疗需要多次手术，这有疤痕形成和面部畸形的风险。最近，利用“无疤痕愈合”的胎儿治疗得到了关注，因为早期干预显示出抑制疤痕形成的潜力。在再生医学领域，利用细胞片的间充质干细胞治疗取得了进展，有望促进组织修复。然而，由于手术侵入性导致胎儿死亡率高，利用小动物模型治疗唇裂的研究具有挑战性。虽然器官培养方法可能提供一种替代方法，但尚未有关于胎儿唇裂器官培养系统研究的报道。方法在E15.5小鼠胎儿左上唇处手术造唇。这些胎儿用器官培养系统培养4天。进行组织学评估以评估细胞密度、组织形态和上皮化情况。此外，脂肪源性干细胞（ADSC）薄片在唇裂形成两天后移植，以评估其对组织修复的影响。结果4 d培养期间细胞密度和组织形态保持稳定。术后2天观察到切口部位上皮化，证实唇裂形成完成。在adsc移植组中，观察到裂隙部位的上皮化，这表明干细胞片有助于组织修复。结论本研究成功地建立了唇裂器官培养模型，突出了ADSC片促进组织修复的潜力。这些发现为未来胎儿唇裂治疗的再生医学策略提供了基础。

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引用次数: 0

Exosomes derived from human placental mesenchymal stem cells in combination with hyperbaric oxygen therapy enhance neuroregeneration in a rat model of sciatic nerve crush injury 来自人胎盘间充质干细胞的外泌体联合高压氧治疗可增强坐骨神经挤压损伤大鼠模型的神经再生

IF 3.4 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2024-11-30 DOI: 10.1016/j.reth.2024.11.021

Fereshteh Talebpour Amiri , Aref Jafari , Fahimeh Ahmadi , Hossein Mokhtari , Amir Raoofi , Farshad Moharrami Kasmaie , Maryam Omran , Mohammad Amin Alimohammadi , Davood Nasiry

Peripheral nerve damage continues to be a significant challenge in the field of medicine, with no currently available effective treatment. Currently, we investigated the beneficial effects of human placenta mesenchymal stem cells (PMSCs)- derived exosomes along with hyperbaric oxygen therapy (HBOT) in a sciatic nerve injury model. Seventy-five male mature Sprague-Dawley rats were allocated into five equal groups. In addition to the control group that received no intervention, damaged animals were allocated into four groups as follows: crush group, exosome group, HBOT group, and Exo+HBOT group. After the last neurological evaluations, tissue samples (sciatic nerve and dorsal root ganglion (DRG)) at the injury side, as well as spinal cord segments related to the sciatic nerve were collected to investigate histological, immunohistochemical, biochemical, and molecular characteristics. We found that the volume of the sciatic nerve, the thickness of the myelin sheath, the densities of nerve fibers and Schwann cells, the numerical densities of sensory neurons and glial cells in the DRG, as well as the numerical density of motor neurons in the anterior horn of the spinal cord, the levels of antioxidative factors (GSH, SOD, and CAT) in the sciatic nerve, as well as the neurological functions (EMG latency and SFI) in the treatment groups, especially the Exo+HBOT group, were significantly improved compared to the crush group. This is while the numerical density of glial cells in the spinal cord, the levels of an oxidative factor (MDA), and pro-inflammatory cytokines (IL-1β, TNF-α, and IFN- γ) considerably decreased in the treatment groups, particularly the Exo+HBOT group, compared to the crush group. We conclude that co-administration of PMSCs-derived exosomes and HBOT has synergistic neuroprotective effects in animals undergoing sciatic nerve injury.

周围神经损伤仍然是医学领域的一个重大挑战，目前尚无有效的治疗方法。目前，我们研究了人胎盘间充质干细胞（PMSCs）来源的外泌体与高压氧治疗（HBOT）在坐骨神经损伤模型中的有益作用。将75只成年雄性Sprague-Dawley大鼠分为5组。在不进行干预的对照组基础上，将损伤动物分为粉碎组、外泌体组、HBOT组、Exo+HBOT组。最后一次神经学评估后，收集损伤侧组织样本（坐骨神经和背根神经节（DRG））以及与坐骨神经相关的脊髓节段，研究组织学、免疫组织化学、生化和分子特征。我们发现坐骨神经的体积,髓鞘的厚度,神经纤维和雪旺细胞的密度,密度数值诊断相关的感觉神经元和神经胶质细胞,以及数值密度脊髓前角运动神经元的,抗氧化因子的水平(谷胱甘肽、SOD和CAT)在坐骨神经,以及神经功能(EMG延迟和SFI)治疗组,尤其是挂式+ HBOT组,与挤压组相比均有显著改善。与挤压组相比，治疗组（尤其是Exo+HBOT组）脊髓胶质细胞的数量密度、氧化因子（MDA）和促炎细胞因子（IL-1β、TNF-α和IFN- γ）的水平显著降低。我们得出结论，pmscs来源的外泌体和HBOT共同给药对坐骨神经损伤动物具有协同的神经保护作用。

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引用次数: 0

Approach of design for air mass balance in an aseptic processing area for cell-based products 细胞类产品无菌加工区的空气质量平衡设计方法

IF 3.4 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2024-11-28 DOI: 10.1016/j.reth.2024.11.009

Shunpei Furomitsu , Manabu Mizutani , Masahiro Kino-oka

Introduction

The manufacture of cell-based products requires assuring sterility through all processes, with aseptic processing in a cleanroom. The environment consists of a critical processing zone (CPZ) that can ensure a level of cleanliness that allows cell culture containers to be opened, and a support zone (SZ) adjacent to it and accessed by an operator. In this study, an environment for cell manufacturing was proposed by designing an air mass balance in an aseptic processing area (APA).

Methods

We considered the distribution of particle concentration related to the airflow of clean air passing through a high efficiency particulate air (HEPA) filter and the location of the particle emission sources and set up a model dividing the SZ into two zones vertically: the upper and lower zones in a cleanroom, considering three cases practically. Both the air inlet and outlet were located outside the cleanroom and were connected to the CPZ directly by air ducts (Case 1). The inlets of the CPZ were located in the lower or upper zones of the SZ inside the cleanroom, and the outlets were located in the upper zone (Case 2 or Case 3, respectively). We analyzed how the cleanliness of the APA was affected by different locations of the inlet and outlet of the CPZ by varying the particle emission rate or air change rate.

Results

In Case 1, changes in the particle emission rate or air change rate within the SZ did not affect the particle concentration in the CPZ. In Case 2, an increase in the particle emission rate led to an increase in the particle concentration of the CPZ. In Case 3, the particle concentration of the CPZ was not affected by the particle emission rate. Cases 2 and 3 showed differences in particle concentrations between the CPZ and SZ, indicating that the location of the air inlet of the CPZ had an impact on the cleanliness of both zones. The partial circulation of air between the SZ and CPZ exhibited an additional air cleaning effect, leading to a reduction in the particle concentration in the SZ in Cases 2 and 3.

Conclusions

These results suggest that the appropriate location of the air inlet and outlet can construct the cleanliness of the APA, which reduces the risk of microbial contamination. In addition, we consider that this approach can realize an APA design policy, which eliminates the need for air ducts between the outside of the cleanroom and the equipment for the CPZ, reduces the requirements for gowning, thereby reducing the required air change rate.

导言细胞产品的生产需要在洁净室中进行无菌处理，以确保所有流程的无菌性。该环境由一个关键处理区（CPZ）和一个辅助区（SZ）组成，前者可确保达到允许打开细胞培养容器的洁净度水平，后者毗邻关键处理区，操作人员可进入辅助区。我们考虑了与通过高效微粒空气过滤器（HEPA）的洁净空气气流有关的微粒浓度分布以及微粒排放源的位置，并建立了一个模型，将 SZ 垂直分为两个区域：洁净室中的上区和下区，并实际考虑了三种情况。进风口和出风口都位于洁净室外部，通过风管直接与 CPZ 相连（情况 1）。CPZ 的进气口位于洁净室内 SZ 的下区或上区，出气口位于上区（分别为情况 2 或情况 3）。我们通过改变粒子排放率或换气率，分析了不同位置的 CPZ 入口和出口对 APA 清洁度的影响。结果在案例 1 中，SZ 内粒子排放率或换气率的变化不会影响 CPZ 中的粒子浓度。在案例 2 中，颗粒排放率的增加导致了 CPZ 中颗粒浓度的增加。在案例 3 中，CPZ 的颗粒浓度不受颗粒排放率的影响。案例 2 和案例 3 显示了 CPZ 和 SZ 之间的颗粒浓度差异，这表明 CPZ 的进气口位置对两个区域的清洁度都有影响。SZ 和 CPZ 之间的部分空气循环具有额外的空气净化效果，导致案例 2 和 3 中 SZ 的颗粒浓度降低。此外，我们认为这种方法可以实现 APA 的设计策略，即无需在洁净室外部和 CPZ 设备之间铺设风管，减少对穿袍的要求，从而降低所需的换气率。

{"title":"Approach of design for air mass balance in an aseptic processing area for cell-based products","authors":"Shunpei Furomitsu , Manabu Mizutani , Masahiro Kino-oka","doi":"10.1016/j.reth.2024.11.009","DOIUrl":"10.1016/j.reth.2024.11.009","url":null,"abstract":"<div><h3>Introduction</h3><div>The manufacture of cell-based products requires assuring sterility through all processes, with aseptic processing in a cleanroom. The environment consists of a critical processing zone (CPZ) that can ensure a level of cleanliness that allows cell culture containers to be opened, and a support zone (SZ) adjacent to it and accessed by an operator. In this study, an environment for cell manufacturing was proposed by designing an air mass balance in an aseptic processing area (APA).</div></div><div><h3>Methods</h3><div>We considered the distribution of particle concentration related to the airflow of clean air passing through a high efficiency particulate air (HEPA) filter and the location of the particle emission sources and set up a model dividing the SZ into two zones vertically: the upper and lower zones in a cleanroom, considering three cases practically. Both the air inlet and outlet were located outside the cleanroom and were connected to the CPZ directly by air ducts (Case 1). The inlets of the CPZ were located in the lower or upper zones of the SZ inside the cleanroom, and the outlets were located in the upper zone (Case 2 or Case 3, respectively). We analyzed how the cleanliness of the APA was affected by different locations of the inlet and outlet of the CPZ by varying the particle emission rate or air change rate.</div></div><div><h3>Results</h3><div>In Case 1, changes in the particle emission rate or air change rate within the SZ did not affect the particle concentration in the CPZ. In Case 2, an increase in the particle emission rate led to an increase in the particle concentration of the CPZ. In Case 3, the particle concentration of the CPZ was not affected by the particle emission rate. Cases 2 and 3 showed differences in particle concentrations between the CPZ and SZ, indicating that the location of the air inlet of the CPZ had an impact on the cleanliness of both zones. The partial circulation of air between the SZ and CPZ exhibited an additional air cleaning effect, leading to a reduction in the particle concentration in the SZ in Cases 2 and 3.</div></div><div><h3>Conclusions</h3><div>These results suggest that the appropriate location of the air inlet and outlet can construct the cleanliness of the APA, which reduces the risk of microbial contamination. In addition, we consider that this approach can realize an APA design policy, which eliminates the need for air ducts between the outside of the cleanroom and the equipment for the CPZ, reduces the requirements for gowning, thereby reducing the required air change rate.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 20-29"},"PeriodicalIF":3.4,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720605","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}

引用次数: 0

Research of in vivo reprogramming toward clinical applications in regenerative medicine: A concise review 研究体内重编程在再生医学中的临床应用：简明综述

IF 3.4 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2024-11-27 DOI: 10.1016/j.reth.2024.11.008

Yoshihiko Nakatsukasa, Yosuke Yamada, Yasuhiro Yamada

The successful generation of induced pluripotent stem cells (iPSCs) has significantly impacted many scientific fields. In the field of regenerative medicine, iPSC-derived somatic cells are expected to recover impaired organ functions through cell transplantation therapy. Subsequent studies using genetically engineered mouse models showed that somatic cells are also reprogrammable in vivo. Notably, cyclic expression of reprogramming factors, so-called partial reprogramming in vivo ameliorates cellular and physiological hallmarks of aging without inducing teratoma formation or premature death of animals. Subsequent studies provided evidence supporting the beneficial effects of partial reprogramming in various organs. Although in vivo reprogramming appears to be a promising strategy for tissue regeneration and rejuvenation, there remain unsolved issues that hinder its clinical application, including concerns regarding its safety, controllability, and unexpected detrimental effects. Here, we review the pathway that research of in vivo reprogramming has followed and discuss the future perspective as we look toward its clinical application in regenerative medicine.

诱导多能干细胞（iPSC）的成功产生对许多科学领域产生了重大影响。在再生医学领域，iPSC 衍生的体细胞有望通过细胞移植疗法恢复受损器官的功能。随后利用基因工程小鼠模型进行的研究表明，体细胞在体内也是可以重编程的。值得注意的是，循环表达重编程因子，即所谓的体内部分重编程，可改善细胞和生理衰老的特征，而不会诱发畸胎瘤形成或动物过早死亡。随后的研究提供了支持部分重编程在各种器官中产生有益影响的证据。虽然体内重编程似乎是一种很有前景的组织再生和年轻化策略，但仍有一些未解决的问题阻碍着它的临床应用，包括对其安全性、可控性和意外的有害影响的担忧。在此，我们回顾了体内重编程研究的发展历程，并探讨了其在再生医学临床应用中的未来前景。

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引用次数: 0

Therapeutic effects of mesenchymal stem cell conditioned media on streptozotocin-induced diabetes in Wistar rats 间充质干细胞条件培养基对链脲佐菌素诱导的 Wistar 大鼠糖尿病的治疗效果

IF 3.4 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2024-11-27 DOI: 10.1016/j.reth.2024.11.004

Marwa S. Shalaby , Eman S. Abdel-Reheim , Taghreed N. Almanaa , Lama Abdulaziz Alhaber , Ahmed Nabil , Osama M. Ahmed , Mariam Elwan , Adel Abdel-Moneim

Cell-based therapy is a new direction of treatment of diseases such as type 1 diabetes mellitus (T1DM); but unfortunately, its severe side effects include immunogenicity and tumor development. Using Mesenchymal stem cells conditioned medium (MSCs-CM) may be an alternative therapy to avoid stem cell risks, preserving effectiveness and demonstrating noticeably increased levels of cytokines, angiogenic factors, and growth factors that encourage and support regenerative processes. In the current work, we examined the effects of MSCs-CM injected in tail vein and pancreas directly compared with the standard antidiabetic drug, glimepiride in streptozotocin-induced type 1 diabetic rats. Fifty adults Male Wistar rats were allocated equally into five groups: normal, diabetic control and three diabetic groups treated respectively with glimepiride, MSCs-CM injected daily into tail vein (MSCs-CMT) and MSCs-CM injected directly in pancreas (MSCs-CMP); all treatments continued for 28 days. The treatments produced a significant improvement in blood glucose level and glycosylated hemoglobin A1c (HbA1c), serum insulin level and lipid panel, and pancreas apoptosis-related markers including B cell lymphoma-2 (Bcl-2) and vimentin. In addition, the treatments resulted in suppression in the oxidation stress and enhancement in the antioxidant, which were manifested by the suppressed lipid peroxidation and the increased antioxidant markers (glutathione, catalase and superoxide dismutase) in the pancreas. In association with the significant decrease in tumour necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) and a signiﬁcant increase in interleukin-10 (IL-10) levels, the inflammatory mediator nuclear factor-kappa B (NF-κB) expression was significantly decreased by MSCs-CMT and MSCs-CMP. The histological amelioration of the pancreatic islet cells assured our study especially in MSCs-CMP group than MSCs-CMT which supports islet regeneration and elevated circulating insulin. These results imply that MSCs-CM infusion has therapeutic benefits in T1DM rats and may be a viable novel therapeutic approach; MSCs-CMP was shown to be more effective than glimepiride and MSCs-CMT. The mechanisms of antidiabtic actions may be mediated via the antioxidant, anti-apoptotic and anti-inflammatory effects.

细胞疗法是治疗1型糖尿病（T1DM）等疾病的新方向；但不幸的是，其严重的副作用包括免疫原性和肿瘤发生。使用间充质干细胞条件培养基（MSCs-CM）可能是一种替代疗法，既能避免干细胞风险，又能保持疗效，还能明显提高细胞因子、血管生成因子和生长因子的水平，促进和支持再生过程。在当前工作中，我们研究了在链脲佐菌素诱导的1型糖尿病大鼠中，将间叶干细胞-CM直接注射到尾静脉和胰腺，与标准抗糖尿病药物格列美脲进行比较的效果。将 50 只成年雄性 Wistar 大鼠平均分为 5 组：正常组、糖尿病对照组和 3 个糖尿病组，分别使用格列美脲、每日尾静脉注射间充质干细胞（间充质干细胞-CMT）和直接在胰腺中注射间充质干细胞（间充质干细胞-CMP）进行治疗；所有治疗均持续 28 天。这些疗法显著改善了血糖水平和糖化血红蛋白 A1c（HbA1c）、血清胰岛素水平和血脂组合，以及胰腺凋亡相关标记物（包括 B 细胞淋巴瘤-2（Bcl-2）和波形蛋白）。此外，治疗还能抑制氧化应激，增强抗氧化能力，具体表现为抑制了胰腺的脂质过氧化反应，增加了抗氧化标志物（谷胱甘肽、过氧化氢酶和超氧化物歧化酶）。在肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）水平显著下降、白细胞介素-10（IL-10）水平显著上升的同时，间充质干细胞-CMT和间充质干细胞-CMP还显著降低了炎症介质核因子-卡巴B（NF-κB）的表达。与间充质干细胞-间充质干细胞治疗组相比，间充质干细胞-间充质干细胞治疗组的胰岛细胞组织学特征明显改善，这支持了胰岛的再生和循环胰岛素的升高。这些结果表明，间充质干细胞-间充质干细胞输注对 T1DM 大鼠有治疗作用，可能是一种可行的新型治疗方法；间充质干细胞-间充质干细胞输注比格列美脲和间充质干细胞-间充质干细胞输注更有效。抗糖尿病作用的机制可能是通过抗氧化、抗凋亡和抗炎作用介导的。

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引用次数: 0

Antler blood enhances the ability of stem cell-derived exosomes to promote bone and vascular regeneration. 鹿茸血增强了干细胞来源的外泌体促进骨和血管再生的能力。

IF 3.4 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2024-11-21 eCollection Date: 2024-06-01 DOI: 10.1016/j.reth.2024.11.003

Renjie Zuo, Quan Liao, Ziwei Ye, Chenchun Ding, Zhenzhen Guo, Junjie He, Guoyan Liu

Background: Bone marrow mesenchymal stem cells (BMSC)-derived exosomes (Exos) are important in promoting bone and vascular regeneration. Antler blood (ALB) is a valuable traditional Chinese medicine with potent regenerative effects. However, there is still a lack of clarity regarding the relationship between ALB and BMSC-Exos.

Methods: Primary BMSCs were isolated from SD Rats, and BMSC-derived Exos (BMSC-Exos) were harvested and identified accordingly. ALB was treated with the solution contained pepsin and hydrochloric acid to simulated gastrointestinal digestion in vitro. Furthermore, the liquid chromatography-mass spectrometry (LC-MS) was performed to determine the components of digested ALB. Moreover, ALB was utilized to intervene on BMSCs to produce specialized Exos (Exos-ALB), of which the angiogenesis functions were detected both in vitro and in vivo. For the potential mechanism, both high-throughput sequencing and proteomics were performed.

Results: The main components of ALB consist of amino acids and peptides. Both ALB and BMSC-Exos exhibited significant promotion of bone and blood vessel formation, respectively. Moreover, ALB and BMSC-Exos could increase the expression of BMP-2, RUNX2, and ALP, but reduce the Osteopontin (OPN) expression. Notably, Exos-ALB exhibited the strongest performance in these functions, whereas the presence of miR-21-5p inhibitor can partially counteract the effects of Exos-ALB. The proteomics reveal differential genes associated with bone minimization, angiogenesis, osteoblast differentiation, vesicle-mediated transport, and the Wnt signaling pathway.

Conclusion: ALB enhances the ability of BMSCs-derived Exos to promote bone and vascular regeneration, which may be related to the up-regulation of miR-21-5p.

背景：骨髓间充质干细胞（BMSC）衍生的外泌体（Exos）在促进骨和血管再生方面具有重要作用。鹿茸血是一种珍贵的中药，具有强大的再生作用。然而，ALB与BMSC-Exos之间的关系尚不明确。方法：从SD大鼠中分离原代BMSCs，收集BMSCs衍生的Exos （BMSCs -Exos）并进行鉴定。用胃蛋白酶和盐酸溶液处理ALB，模拟体外胃肠道消化。同时，采用液相色谱-质谱联用法测定消化后ALB的成分。此外，利用ALB干预骨髓间充质干细胞生成特异性Exos (Exos-ALB)，体外和体内均检测到其血管生成功能。对于潜在的机制，我们进行了高通量测序和蛋白质组学研究。结果：ALB的主要成分为氨基酸和多肽。ALB和BMSC-Exos均能显著促进骨和血管的形成。此外，ALB和BMSC-Exos可增加BMP-2、RUNX2和ALP的表达，而降低骨桥蛋白（OPN）的表达。值得注意的是，Exos-ALB在这些功能中表现出最强的性能，而miR-21-5p抑制剂的存在可以部分抵消Exos-ALB的作用。蛋白质组学揭示了与骨最小化、血管生成、成骨细胞分化、囊泡介导的运输和Wnt信号通路相关的差异基因。结论：ALB增强bmscs来源的Exos促进骨和血管再生的能力，这可能与miR-21-5p的上调有关。

{"title":"Antler blood enhances the ability of stem cell-derived exosomes to promote bone and vascular regeneration.","authors":"Renjie Zuo, Quan Liao, Ziwei Ye, Chenchun Ding, Zhenzhen Guo, Junjie He, Guoyan Liu","doi":"10.1016/j.reth.2024.11.003","DOIUrl":"10.1016/j.reth.2024.11.003","url":null,"abstract":"<p><strong>Background: </strong>Bone marrow mesenchymal stem cells (BMSC)-derived exosomes (Exos) are important in promoting bone and vascular regeneration. Antler blood (ALB) is a valuable traditional Chinese medicine with potent regenerative effects. However, there is still a lack of clarity regarding the relationship between ALB and BMSC-Exos.</p><p><strong>Methods: </strong>Primary BMSCs were isolated from SD Rats, and BMSC-derived Exos (BMSC-Exos) were harvested and identified accordingly. ALB was treated with the solution contained pepsin and hydrochloric acid to simulated gastrointestinal digestion <i>in vitro</i>. Furthermore, the liquid chromatography-mass spectrometry (LC-MS) was performed to determine the components of digested ALB. Moreover, ALB was utilized to intervene on BMSCs to produce specialized Exos (Exos-ALB), of which the angiogenesis functions were detected both <i>in vitro</i> and <i>in vivo</i>. For the potential mechanism, both high-throughput sequencing and proteomics were performed.</p><p><strong>Results: </strong>The main components of ALB consist of amino acids and peptides. Both ALB and BMSC-Exos exhibited significant promotion of bone and blood vessel formation, respectively. Moreover, ALB and BMSC-Exos could increase the expression of BMP-2, RUNX2, and ALP, but reduce the Osteopontin (OPN) expression. Notably, Exos-ALB exhibited the strongest performance in these functions, whereas the presence of miR-21-5p inhibitor can partially counteract the effects of Exos-ALB. The proteomics reveal differential genes associated with bone minimization, angiogenesis, osteoblast differentiation, vesicle-mediated transport, and the Wnt signaling pathway.</p><p><strong>Conclusion: </strong>ALB enhances the ability of BMSCs-derived Exos to promote bone and vascular regeneration, which may be related to the up-regulation of miR-21-5p.</p>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"26 ","pages":"1168-1180"},"PeriodicalIF":3.4,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786424","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}

引用次数: 0

HUC-MSCs combined with platelet lysate treat diabetic chronic cutaneous ulcers in Bama miniature pig. HUC-MSCs联合血小板裂解液治疗巴马小型猪糖尿病性慢性皮肤溃疡。

IF 3.4 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2024-11-20 eCollection Date: 2024-06-01 DOI: 10.1016/j.reth.2024.11.005

Yunyi Gao, Lihong Chen, Yan Li, Shiyi Sun, XingWu Ran

Human umbilical cord mesenchymal stem cells (HUC-MSCs) and platelet lysate (PL) shows potential of wound healing. However, MSCs in combination with PL for wound healing is still lacking. In this study, we presented high glucose cultured wound related cells to mimic diabetic chronic ulcers (DCU) cells, wound healing indicators and the TGFβ/Smad signaling pathway were detected by PL cultured HUC-MSC supernatant (MSC-Sp) in vitro. In vivo study, diabetes was induced in pigs feeding a high-energy diet and multiple injections of streptozotocin (125 mg/kg). Chronic wounds were created on both sides of the backs of seven pigs by surgical creation and foreign body compression for eight weeks before treatment. The wounds were treated with saline control (N = 11), PL (N = 11), HUC- MSCs (N = 18, 6 × 10⁶/mL/cm²), and PL + HUC-MSCs (N = 18, 6 × 10⁶/mL/cm²) respectively. Tissue samples were collected to observe new collagen, neovascularization, wound healing factors, and the TGFβ/Smad signaling pathway. The resulting PL-cultured MSC-Sp promoted the proliferation of keratinocytes, fibroblasts, and vascular endothelial cells and inhibited the TGFβ1/TGFβ3 ratio, upregulated VEGF-α and PDGF-BB production by keratinocytes and fibroblasts, and downregulated the expression of CD86, IL-6, and TNF-α in RAW264.7 cells. PL + HUC-MSCs had the best wound healing rate in vivo, and promoted collagen formation, neovascularization, and inflammation, regulated the balance between IL-6/TGFβ1 and IL-6/Arg-1 and upregulated the expression of VEGF-α and TGFβ1. In summary, PL + HUC-MSCs had a better wound healing effect than HUC-MSCs or PL treatment alone by regulating the IL-6/Arg-1 and IL-6/TGFβ1 balance and upregulating TGFβ1, VEGF-α, Col1, and α-SMA.

人脐带间充质干细胞（HUC-MSCs）和血小板裂解液（PL）显示出伤口愈合的潜力。然而，MSCs联合PL用于伤口愈合仍然缺乏。本研究采用高糖培养的创面相关细胞模拟糖尿病慢性溃疡（DCU）细胞，采用体外培养的HUC-MSC上清（MSC-Sp）检测创面愈合指标和TGFβ/Smad信号通路。在体内试验中，采用高能量饲粮和多次注射链脲佐菌素（125 mg/kg）诱导猪患糖尿病。在治疗前8周，通过手术创面和异物压迫在7头猪的背部两侧形成慢性伤口。分别用生理盐水对照（N = 11）、PL （N = 11）、HUC-MSCs （N = 18、6 × 106/mL/cm2）和PL + HUC-MSCs （N = 18、6 × 106/mL/cm2）处理创面。收集组织样本，观察新生胶原、新生血管、创面愈合因子和TGFβ/Smad信号通路。由此得到的pl培养的MSC-Sp促进角质形成细胞、成纤维细胞和血管内皮细胞的增殖，抑制tgf - β1/ tgf - β3比值，上调角质形成细胞和成纤维细胞的VEGF-α和PDGF-BB的产生，下调RAW264.7细胞中CD86、IL-6和TNF-α的表达。PL + HUC-MSCs具有最佳的体内创面愈合率，促进胶原形成、新生血管形成和炎症反应，调节IL-6/ tgf - β1和IL-6/Arg-1的平衡，上调VEGF-α和tgf - β1的表达。综上所述，PL + HUC-MSCs通过调节IL-6/Arg-1和IL-6/ tgf - β1的平衡，上调tgf - β1、VEGF-α、Col1和α-SMA，其创面愈合效果优于HUC-MSCs或PL单独处理。

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引用次数: 0

Stem cell assisted low-intensity shockwave for erectile dysfunction treatment: Current perspective. 干细胞辅助低强度冲击波治疗勃起功能障碍：目前的观点。

IF 3.4 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2024-11-20 eCollection Date: 2024-06-01 DOI: 10.1016/j.reth.2024.11.006

Datesh Daneshwar, Yemin Lee, Abid Nordin

Stem cell therapy and low-intensity extracorporeal shockwave (LI-ECSW) are recognized as potential restorative therapies and have been used in the treatment of erectile dysfunction (ED). Stem cell therapy is well-known due to its attributed regenerative ability and thus can help to improve erectile function in patients with vasculogenic ED. Besides, current evidence also shows that LI-ECSW therapy can help stimulate cell recruitment and proliferation and promote angiogenesis and vascularization in the damaged tissue. Hence, due to the therapeutic and restorative effects of both therapies, the success of ED treatment can be elevated through a combination therapy between stem cell therapy and LI-ECSW. In this review, a detailed description and efficacy discussion of combination therapies between different types of stem cells and LI-ECSW therapy are described. Besides, other potential cell types to use together with LI-ECSW are also listed in this review. Thus, this review provides better insight on the efficacy of combination therapy for ED treatment.

干细胞疗法和低强度体外冲击波（LI-ECSW）被认为是潜在的恢复性疗法，并已被用于治疗勃起功能障碍（ED）。干细胞治疗因其再生能力而闻名，因此可以帮助改善血管源性ED患者的勃起功能。此外，目前的证据还表明，LI-ECSW治疗可以帮助刺激细胞募集和增殖，促进受损组织的血管生成和血管化。因此，由于两种疗法的治疗和恢复作用，可以通过干细胞治疗和LI-ECSW的联合治疗来提高ED治疗的成功率。在这篇综述中，详细描述了不同类型的干细胞和LI-ECSW联合治疗的疗效讨论。此外，本文还列出了其他可能与LI-ECSW一起使用的电池类型。因此，本综述对联合治疗ED的疗效提供了更好的见解。

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引用次数: 0

Insight of the interrelationship and association mechanism between periodontitis and diabetes mellitus. 牙周炎与糖尿病的相互关系及相关机制研究。

IF 3.4 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING

Regenerative Therapy

Pub Date : 2024-11-20 eCollection Date: 2024-06-01 DOI: 10.1016/j.reth.2024.11.001

Yongqiang Yang, Xia Sun, Yucheng Yang, Yingchun Qie

Periodontitis and diabetes mellitus are two prevalent chronic diseases that have been recognized to exhibit a bidirectional relationship. Individuals with diabetes are more susceptible to periodontitis, and conversely, periodontitis can exacerbate glycemic control in diabetic patients. The underlying mechanisms of this interrelationship involve complex pathways, including inflammatory responses, altered immune functions, and microbial dysbiosis. The mechanistic insights into the interrelationship between periodontitis and diabetes mellitus revolve around the role of inflammation as a common link between the two diseases. Inflammatory mediators such as cytokines, chemokines, and prostaglandins play a crucial role in the pathogenesis and progression of the diseases. The dysregulation of the immune response in diabetes can exacerbate the inflammatory response in periodontitis, leading to increased tissue destruction and bone resorption. The chronic inflammation in periodontitis can contribute to insulin resistance and impaired glycemic control in diabetic patients. Future directions in research aim to further elucidate the molecular mechanisms underlying the interrelationship between periodontitis and diabetes mellitus. Modulating the inflammatory response, restoring microbial balance, and improving glycemic control hold promise in managing both conditions simultaneously. Herein, we will provide an overview of the interrelationship of periodontitis and diabetes mellitus, and retrospect the underlying mechanisms, which may inspire investigators with further research directions.

牙周炎和糖尿病是两种常见的慢性疾病，已被公认为具有双向关系。糖尿病患者更容易患牙周炎，相反，牙周炎会加剧糖尿病患者的血糖控制。这种相互关系的潜在机制涉及复杂的途径，包括炎症反应、免疫功能改变和微生物生态失调。对牙周炎和糖尿病之间相互关系的机制见解围绕着炎症作为两种疾病之间的共同联系的作用。炎症介质如细胞因子、趋化因子和前列腺素在疾病的发病和进展中起着至关重要的作用。糖尿病患者的免疫反应失调会加剧牙周炎的炎症反应，导致组织破坏和骨吸收增加。慢性牙周炎可导致糖尿病患者胰岛素抵抗和血糖控制受损。未来的研究方向是进一步阐明牙周炎与糖尿病相互关系的分子机制。调节炎症反应、恢复微生物平衡和改善血糖控制有望同时控制这两种疾病。本文就牙周炎与糖尿病的相互关系作一综述，并对其发病机制进行回顾，以期对今后的研究方向有所启发。

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引用次数: 0