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Mesenchymal stem/stromal cells (MSCs) are adult multipotent cells with self-renewal potential and the ability to differentiate into specialized cells. MSCs home in various tissues and can be isolated using simple methods. Because of this feasibility in the isolation and culture of MSCs in vitro, many scientists have focused on the therapeutic applications of MSCs for various diseases and conditions. The selection of the tissue source to obtain MSCs mainly depends on the availability of the tissue, the patient’s health status, as well as the expertise of the researcher. However, some studies indicate that MSCs derived from different tissue sources are not the same and possess different regenerative capacities. Therefore, in this review, we have collected and summarized the results from studies that have performed head-to-head comparisons between MSCs isolated from different tissues. Despite the assessment method discrepancy between studies, results from these studies reveal that MSCs derived from different tissue sources are not the same. Some such as umbilical cord-derived MSCs and menstrual blood-derived MSCs were identified with robust angiogenic potentials. However, cord blood-derived MSCs possessed a strong cartilage repair capacity. Further investigations are required to establish certain capabilities for MSCs derived from a particular tissue origin. Nevertheless, it is recommended to consider the possibility of functional variations between MSCs isolated from distinct tissue origins when applying MSCs in clinics.

Menstrual blood is a rich source of mesenchymal stem/stromal cells (MenSCs) with a diverse potential to differentiate into various cell types. Similar to other cells, MenSCs produce extracellular vesicles from which, small extracellular vesicles have attracted much interest due to their therapeutic and regenerative capacities. Here using in vitro approaches, several properties of MenSC-derived small extracellular vesicles (MEX) have been investigated. HUVEC angiogenesis assay was used to evaluate the proangiogenic function of MEX. The immune regulatory property of MEX was assessed using a T cell proliferation assay. Proliferation, migration, and gene expression of primary fibroblasts were selected to determine the scar-related activity of MEX. Finally, the anti-cancer effect of MEX on the proliferation of cancerous cell lines was tested. Our results demonstrated that the small extracellular vesicles isolated from MenSCs have proangiogenic and immune-suppressive abilities. Moreover, these vesicles performed as an anti-proliferative agent for cancerous cell lines. MEX was also able to reduce the migration of primary fibroblasts. In summary, MEX has shown promising in vitro characteristics for regenerative applications. They may offer a great cell-free strategy with therapeutic potential for a diverse range of diseases. For future therapeutic applications and further clinical translation, more studies are needed to elucidate the involved mechanisms.

Type 1 diabetes, has been recognized as an autoimmune disease. Like other immunological conditions, regulation of immune response is a key strategy to control the autoimmunity in diabetic patients. Mesenchymal stem cells have been shown to have a distinct potential in modulating the immune reactions. However, treatment with stem cells is combined with concerns about safety issues. To overcome these concerns, in this study, we have utilized the regenerative potential of exosomes isolated from menstrual blood-derived mesenchymal stem cells to restore the β-cell mass and insulin production in type 1 diabetes. Exosomes are nanovesicles containing various cargos involved in cellular communications. Streptozotocin was used to induce islet destruction and diabetes in male Wistar rats. Then, exosomes were intravenously injected into animals at different time points and in a single or repeated therapeutic doses. After about 6 weeks, animals were euthanized and the pancreas was analyzed for the presence of the regenerated β islets as well as the insulin secretion. The non-fasting blood glucose and the serum insulin level were also monitored during the study. Our results represented that menstrual blood-derived mesenchymal stem cell-derived exosomes enhance the β-cell mass and insulin production in the pancreas of diabetic animals that received repeated doses of exosomes. Immunohistochemistry analysis also confirmed the presence of insulin in the islets of treated animals. Further investigations proposed that exosomes induce the islet regeneration through pancreatic and duodenal homeobox 1 pathway. The exosome tracking also revealed the homing of injected exosomes to the pancreas.

Aim: Proper healing of extensive burns remains a healthcare challenge. In the present study, we proposed a distinct therapeutic application of adipose tissue and small extracellular vesicles isolated from human menstrual blood-derived mesenchymal stem cells (MenSC) small extracellular vesicles (sEVs) to enhance the repair of third-degree burn injury. Materials & methods: Mouse model of third-degree burn was used. Adipose tissue in the form of nano-fat (NF) and MenSC-sEVs was injected subcutaneously at the site of injuries. Results: NF and sEVs were capable of enhancing wound closure and increasing neoangiogenesis. NF was also effective in accelerating the formation of granulation tissue and boosting the thickness of the new epithelial layer. Conclusion: This study demonstrates the effectiveness of NF and MenSC-sEVs as promising therapeutic approaches to facilitate the repair of skin burns.

Cell-based delivery system is a promising strategy to protect therapeutic agents from the immune system and provide targeted delivery. Mesenchymal stem cells (MSCs) have recently been introduced as an encouraging vehicle in cell-based gene therapy due to their unique features including tumor-tropic property and migratory ability. However, gene transfer into MSCs is limited due to low efficiency and cytotoxicity of carriers. In this study, we designed a novel delivery system based on polyethylenimine (PEI25 ) to improve these features of carrier and transfect plasmid encoding TRAIL to MSCs. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand of TNF family with selective effect on cancerous cells. Then, death induction and migration ability of TRAIL-expressing MSCs was studied in melanoma cells. The effect of engineered-MSCs as an antitumor vehicle was also investigated in mice bearing melanoma cells. Our findings indicated that heterocyclic amine derivative of PEI25 showed significant improvement in MSCs viability determined by MTT assay and gene expression using fluorescent microscopy, flow cytometry, and Western blot analysis. We observed that engineered-MSCs could migrate toward and induce cell death in B16F0 cells in vitro. The single administration of TRAIL-expressing MSCs could delay tumor appearance and efficiently reduce tumor weights. Hematoxylin and eosin staining of tumor sections revealed extensive neoplastic cells necrosis. Furthermore, engineered-MSCs could migrate and localize to tumors sites within 5 days. Our results indicated that MSCs engineered by modified-PEI/TRAIL complexes could be considered as a promising cellular vehicle for targeted tumor suppression.

Wound healing is a complicated process that contains a number of overlapping and consecutive phases, disruption in each of which can cause chronic nonhealing wounds. In the current study, we investigated the effects of exosomes as paracrine factors released from menstrual blood-derived mesenchymal stem cells (MenSCs) on wound-healing process in diabetic mice. The exosomes were isolated from MenSCs conditioned media using ultracentrifugation and were characterized by scanning electron microscope and western blotting assay. A full thickness excisional wound was created on the dorsal skin of each streptozotocin-induced diabetic mouse. The mice were divided into three groups as follows: phosphate buffered saline, exosomes, and MenSC groups. We found that MenSC-derived exosomes can resolve inflammation via induced M1-M2 macrophage polarization. It was observed that exosomes enhance neoangiogenesis through vascular endothelial growth factor A upregulation. Re-epithelialization accelerated in the exosome-treated mice, most likely through NF-κB p65 subunit upregulation and activation of the NF-κB signaling pathway. The results demonstrated that exosomes possibly cause less scar formation through decreased Col1:Col3 ratio. These notable results showed that the MenSC-derived exosomes effectively ameliorated cutaneous nonhealing wounds. We suggest that exosomes can be employed in regenerative medicine for skin repair in difficult-to-heal conditions such as diabetic foot ulcer.

Background Mesenchymal stem cells (MSCs) are currently the most promising candidates in regenerative medicine. Nonetheless, there are several limitations associated with the MSC tissue source such as infrequent and invasive bone marrow sampling methods. To overcome these limitations, we have procured MSCs from the menstrual blood (MenSCs) as a non-invasive source using a straightforward and cost-effective method. Moreover, we isolated MenSCs-derived exosomes as a safe and highly effective approach to exert the paracrine effects of MSCs. Methods MSCs were isolated from menstrual blood through two different culture methods: ficoll-isolated mononuclear cells (MNCs) and whole blood culture. These cells were characterized by their plastic adherence, flow cytometry analysis of the surface markers and the differentiation potential. The exosomes were isolated from conditioned media using ultracentrifugation and characterized by different microscopy techniques, western blotting, and ELISA. Results Both Methods resulted in the rapid isolation of cells with MSC properties. However, the cellular yield of the whole blood culture method was remarkably more than MNCs culture. MenSCs also produced a substantial amount of extracellular vesicles (EVs) possessed the minimum criteria for exosome definition. Conclusion The results suggest that direct culture of whole menstrual blood cells is a high throughput, straightforward and cost-effective method for MenSCs isolation using no special growth factors. Moreover, these cells are a good producer of exosome which can offer a cell-free therapy approach.

Stroke, as the second most common cause of death, imposes a great financial burden on both the individual and society. Mesenchymal stem cells from rodents have demonstrated efficacy in experimental animal models of stroke due to enhanced neurological recovery. Since FGF1 (fibroblast growth factor 1) displays neuroprotective properties, for the first time, we investigated the effect of acute intravenous administration of FGF1 gene transfected adipose-derived mesenchymal stem cell (AD-MSC

The aim of this study was to investigate, for the first time, the effects of using adipose-derived mesenchymal stem cells (AD-MSCs) transfected with an episomal plasmid encoding fibroblast growth factor 1 (FGF1) (AD-MSCsFGF1), in providing the microenvironment required for angiogenic proliferation. The isolated rat AD-MSCs were positive for mesenchymal (CD29 and CD90) and negative for hematopoietic (CD34 and CD45) surface markers. Adipogenic and osteogenic differentiation of the AD-MSCs also occurred in the proper culture media. The presence of FGF1 in the conditioned medium from the AD-MSCsFGF1 was confirmed by Western blotting. G418 and PCR were used for selection of transfected cells and confirmation of the presence of FGF1 mRNA, respectively. Treatment with the AD-MSCFGF1-conditioned medium significantly increased the NIH-3T3 cell proliferation and human umbilical vein endothelial cell (HUVEC) tube formation compared to conditioned medium from nontransfected AD-MSCs (p