Regenerative Therapy最新文献

{"title":"Platelet-rich plasma combined with isometric quadriceps contraction regulates autophagy in chondrocytes via the PI3K/AKT/mTOR pathway to promote cartilage repair in knee osteoarthritis","authors":"Liang Cheng ,&nbsp;Shuwan Chang ,&nbsp;Yajun Tan ,&nbsp;Benxiang He","doi":"10.1016/j.reth.2024.11.013","DOIUrl":"10.1016/j.reth.2024.11.013","url":null,"abstract":"<div><h3>Background</h3><div>This study investigated the molecular mechanism by which the combination of platelet-rich plasma (PRP) and isometric contraction of the quadriceps (ICQ) intervention regulates autophagy in chondrocytes to prevent and treat knee osteoarthritis (KOA).</div></div><div><h3>Methods</h3><div>Thirty Sprague-Dawley rats were divided into a control group (CG, n = 6) and a model group (n = 24). After one week, the model group was randomly divided into a joint intervention group (JIG), a rapamycin group (RAG), an MHY1485 group (MYG), and a model blank group (MBG), with JIG, RAG, and MYG receiving the same combined intervention.</div></div><div><h3>Results</h3><div>The trend of cartilage lesions in each group was CG &lt; RAG &lt; JIG &lt; MYG &lt; MBG. Compared with MBG and MYG, JIG and RAG showed downregulation of IL-1β, IL-6, IL-18, MMP-13, and TNF-α mRNA in the cartilage (<em>p</em> &lt; 0.01); mTOR protein expression: compared with JIG, RAG showed downregulation, and MYG showed upregulation. Compared with RAG, MYG showed upregulation (<em>p</em> &lt; 0.01); ATG5 protein expression: compared with RAG, MYG showed downregulation (<em>p</em> &lt; 0.01); Beclin1, LC3-I, and ULK1 protein expression: compared with JIG, RAG showed upregulation, and MYG showed downregulation (<em>p</em> &lt; 0.01). Compared with RAG, MYG showed downregulation (<em>p</em> &lt; 0.01); P62 protein expression: compared with RAG, both MBG and RAG showed upregulation, and MYG showed downregulation (<em>p</em> &lt; 0.05); LC3-II/LC3-I ratio: compared with JIG and RAG, the ratio in MYG was decreased (<em>p</em> &lt; 0.01).</div></div><div><h3>Conclusion</h3><div>The combined intervention promotes autophagy in chondrocytes by inhibiting the PI3K/AKT/mTOR pathway, downregulating inflammatory factors and MMP-13 in the cartilage, upregulating autophagy markers, inhibiting matrix degradation, and promoting cartilage repair.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 81-89"},"PeriodicalIF":3.4,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865346","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}

{"title":"Cleaning methods for biosafety cabinet to eliminate residual mycoplasmas, viruses, and endotoxins after changeover","authors":"Mitsuru Mizuno ,&nbsp;Saeri Kimbara ,&nbsp;Hanae Ichise ,&nbsp;Natsumi Ishikawa ,&nbsp;Yuto Nishihara ,&nbsp;Miwako Nishio ,&nbsp;Ichiro Sekiya","doi":"10.1016/j.reth.2024.11.020","DOIUrl":"10.1016/j.reth.2024.11.020","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Cell-processing operations can potentially contaminate biosafety cabinets, which should be maintained sterile. However, unintended contamination can occur owing to the presence of viruses, mycoplasmas, and bacteria in the raw materials. Moreover, although several methods for expunging these contaminants have been proposed, an optimal method has not yet been determined. Additionally, the effectiveness of conventional methods for eliminating these contaminants remains unclear owing to their unique characteristics and potential resistances to cleaning. Therefore, this paper proposes a risk-based approach to identify appropriate cleaning methods and reduce the likelihood of cross-contamination in biosafety cabinets by these contaminants.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Various cleaning methods for eliminating mycoplasmas, viruses, and endotoxins from biosafety cabinets were evaluated, including ultraviolet (UV) irradiation at 200 mJ/cm&lt;sup&gt;2&lt;/sup&gt; for 20 min and wiping with disinfectants such as distilled water, benzalkonium chloride (BKC), and 70 % ethanol (ETH). The effectiveness of each method was evaluated by applying the contaminants on stainless steel plates and cleaning them using each method. &lt;em&gt;Mycoplasma orale&lt;/em&gt; was cultured for 2 weeks in a liquid medium after cleaning. &lt;em&gt;Feline calicivirus&lt;/em&gt; (FCV) was used for evaluating the virus-cleaning effectiveness and its presence was tested using the TCID50 test, whereas endotoxins obtained from the dried extract of &lt;em&gt;Escherichia coli&lt;/em&gt; were measured via endotoxin testing.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;UV irradiation and wiping with BKC inhibited the growth of mycoplasma and significant decreased their presence compared with the other cleaning methods. Notably, mycoplasma were detected after wiping all SUS304 plates with ETH, which is a widely used cleaning method. Additionally, the cleaning efficacy for virus showed that the TCID&lt;sub&gt;50&lt;/sub&gt; of the wet group was 132,000 TCID&lt;sub&gt;50&lt;/sub&gt;/plate, whereas those after UV irradiation or cleaning with BKC or DW were below the detection limit. Finally, UV irradiation did not significantly reduce the endotoxin production compared with that in the dry group. Additionally, wiping with ETH did not significantly reduce endotoxins compared with the dry group and their residues were higher than those detected after wiping with BKC or DW.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;The changeover protocols currently employed in most cell-processing facilities may be ineffective as pathogenic or nonpathogenic materials may remain even after ETH wiping, leading to unintended cross-contamination. To the best of our knowledge, this is the first study to provide reference data of different cleaning methods for mycoplasmas, viruses, and endotoxins in cell-product manufacturing facilities, and can potentially support the development of evidence-based management strategies for ensuring safe cell-product processing.&lt;","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 73-80"},"PeriodicalIF":3.4,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865340","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}

{"title":"Nanocurcumin-enhanced zein nanofibers: Advancing macrophage polarization and accelerating wound healing","authors":"Mohammad Ebrahim Astaneh ,&nbsp;Narges Fereydouni","doi":"10.1016/j.reth.2024.11.016","DOIUrl":"10.1016/j.reth.2024.11.016","url":null,"abstract":"<div><h3>Introduction</h3><div>Chronic wounds continue to pose a significant global challenge, incurring substantial costs and necessitating extensive research in wound healing. Our previous work involved synthesizing zein nanofibers embedded with 5 %, 10 %, and 15 % nano-curcumin (Zein/nCUR 5, 10, and 15 % NFs), and examining their physicochemical and biological properties. This study aims to explore the potential of these nanofibers in macrophage (MØ) polarization and wound healing.</div></div><div><h3>Methods</h3><div>We assessed the survival of RAW264.7 cells cultured on Zein/nCUR 5, 10, and 15 % NFs using the MTT assay. To evaluate MØ polarization, we measured the expression of iNOS and Arg-1 genes in MØs cultured on Zein/nCUR 10 % NFs through real-time PCR. Furthermore, we examined the nanofibers' impact on pro-inflammatory cytokine expression (IL-1β, IL-6, TNF-α) in MØs via real-time PCR. The wound healing efficacy of Zein/nCUR 10 % NFs was tested on 54 male rats with full-thickness wounds, with assessments conducted on days 3, 7, and 14. Wound closure, re-epithelialization, and collagen secretion were evaluated through photographic analysis and tissue staining. Statistical analyses were performed using GraphPad Prism 6, with significance set at <em>p</em> &lt; 0.05.</div></div><div><h3>Results</h3><div>Zein/nCUR 10 % NFs significantly enhanced the survival of RAW264.7 cells compared to other groups. They also markedly reduced iNOS expression and increased Arg-1 expression, indicating successful polarization of M1 to M2 MØs. Additionally, these nanofibers decreased the expression of IL-1β, IL-6, and TNF-α, and significantly improved wound closure, re-epithelialization, and collagen deposition compared to control and Zein groups.</div></div><div><h3>Conclusions</h3><div>This study demonstrates that Zein/nCUR 10 % NFs effectively polarize MØs from M1 to M2, significantly enhancing wound healing, thus offering a promising therapeutic approach for improved wound care.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 51-62"},"PeriodicalIF":3.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142758836","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}

{"title":"Establishment of feline embryonic stem cells from the inner cell mass of blastocysts produced in vitro","authors":"Takumi Yoshida ,&nbsp;Masaya Tsukamoto ,&nbsp;Kazuto Kimura ,&nbsp;Miyuu Tanaka ,&nbsp;Mitsuru Kuwamura ,&nbsp;Shingo Hatoya","doi":"10.1016/j.reth.2024.11.010","DOIUrl":"10.1016/j.reth.2024.11.010","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>In this study, we isolated three inner cell masses from feline <em>in vitro</em>-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.</div></div><div><h3>Results</h3><div>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 <em>in vitro</em>. Immunostaining and flow cytometry analysis demonstrated that feline ESCs express undifferentiated marker proteins <em>in vitro</em>. 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 <em>de novo</em> pluripotency <em>in vivo</em>. We also verified that the feline ESCs maintained a normal karyotype.</div></div><div><h3>Conclusions</h3><div>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 <em>in vitro</em>.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 63-72"},"PeriodicalIF":3.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759440","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}

{"title":"Establishment of a mouse organ culture model of fetal cleft lip for the evaluation of adipose-derived stem cell therapy","authors":"Ayane Fukutome ,&nbsp;Tomoaki Sakamoto ,&nbsp;Yukiyo Asawa ,&nbsp;Dan Riu ,&nbsp;Hiroshi Kawakami ,&nbsp;Kazuto Hoshi ,&nbsp;Atsuhiko Hikita","doi":"10.1016/j.reth.2024.11.012","DOIUrl":"10.1016/j.reth.2024.11.012","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 41-50"},"PeriodicalIF":3.4,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746974","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}

{"title":"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","authors":"Fereshteh Talebpour Amiri ,&nbsp;Aref Jafari ,&nbsp;Fahimeh Ahmadi ,&nbsp;Hossein Mokhtari ,&nbsp;Amir Raoofi ,&nbsp;Farshad Moharrami Kasmaie ,&nbsp;Maryam Omran ,&nbsp;Mohammad Amin Alimohammadi ,&nbsp;Davood Nasiry","doi":"10.1016/j.reth.2024.11.021","DOIUrl":"10.1016/j.reth.2024.11.021","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 30-40"},"PeriodicalIF":3.4,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142747098","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}

{"title":"Approach of design for air mass balance in an aseptic processing area for cell-based products","authors":"Shunpei Furomitsu ,&nbsp;Manabu Mizutani ,&nbsp;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}

{"title":"Research of in vivo reprogramming toward clinical applications in regenerative medicine: A concise review","authors":"Yoshihiko Nakatsukasa,&nbsp;Yosuke Yamada,&nbsp;Yasuhiro Yamada","doi":"10.1016/j.reth.2024.11.008","DOIUrl":"10.1016/j.reth.2024.11.008","url":null,"abstract":"<div><div>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 <em>in vivo</em>. Notably, cyclic expression of reprogramming factors, so-called partial reprogramming <em>in vivo</em> 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 <em>in vivo</em> 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 <em>in vivo</em> reprogramming has followed and discuss the future perspective as we look toward its clinical application in regenerative medicine.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 12-19"},"PeriodicalIF":3.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720603","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}

{"title":"Therapeutic effects of mesenchymal stem cell conditioned media on streptozotocin-induced diabetes in Wistar rats","authors":"Marwa S. Shalaby ,&nbsp;Eman S. Abdel-Reheim ,&nbsp;Taghreed N. Almanaa ,&nbsp;Lama Abdulaziz Alhaber ,&nbsp;Ahmed Nabil ,&nbsp;Osama M. Ahmed ,&nbsp;Mariam Elwan ,&nbsp;Adel Abdel-Moneim","doi":"10.1016/j.reth.2024.11.004","DOIUrl":"10.1016/j.reth.2024.11.004","url":null,"abstract":"<div><div>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 <em>via</em> the antioxidant, anti-apoptotic and anti-inflammatory effects.</div></div>","PeriodicalId":20895,"journal":{"name":"Regenerative Therapy","volume":"28 ","pages":"Pages 1-11"},"PeriodicalIF":3.4,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720602","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}

{"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}