Apoptosis releases numerous apoptotic vesicles that regulate processes such as cell proliferation, immunity, and tissue regeneration and repair. Now, it has also emerged as an attractive candidate for biotherapeutics. However, apoptotic vesicles encompass a diverse range of subtypes, and it remains unclear which specific subtypes play a pivotal role. In this study, we successfully isolated different apoptotic vesicle subtypes based on their sizes and characterized them using NTA and TEM techniques, respectively. We compared the functional variances among the distinct subtypes of apoptotic vesicles in terms of stem cell proliferation, migration, and differentiation, as well as for endothelial cell and macrophage function, effectively identifying subtypes that exhibit discernible functional differences. ApoSEV (with diameter <1000 nm) promoted stem cell proliferation, migration, and multi-potent differentiation, and accelerated skin wound healing of diabetes mouse model, while apoBD (with diameter >1000 nm) played the opposite effect on cell function and tissue regeneration. Lastly, employing protein analysis and gene sequencing techniques, we elucidated the intrinsic mechanisms underlying these differences between different subtypes of apoEVs. Collectively, this study identified that apoptotic vesicle subtypes possessed distinct bio-functions in regulating stem cell function and behaviour and modulating tissue regeneration, which primarily attribute to the distinct profiling of protein and mRNA in different subtypes. This comprehensive analysis of specific subtypes of apoEVs would provide novel insights for potential therapeutic applications in cell biology and tissue regeneration.
© 2024 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.

A Erectile dysfunction (ED) is one of the well-known comorbidities in males with diabetes mellitus (DM), whose pathogenesis might be induced by dysregulation of corpus cavernosum smooth muscle cells. UC-MSCs are multipotent cells that attract considerable interest due to immunoregulatory properties and might be a potential strategy to regulate and recover the functional cells and tissues, including tissue improvement in DMED.
This study aims to determine the efficacy of UC-MSCs in improving the erectile function of DMED rats through analyzing the expression of TGF-β, α-SMA, and collagen.
Total number of 30 male Sprague-Dawley rats (6 to 8 weeks old) were randomly divided into four groups (negative control group, positive control group, T1 group, and T2 group). After 16 h fast, 24 rats were randomly selected and intraperitoneally injected with streptozotocin to induce DM. At 8 weeks after STZ injection, rats with DMED were identified by unresponsive erectile stimulation within 30 min. PC group received 500 μL; T1 rats treated with 500 μL PBS containing 1x106 UC-MSCs; T2 rats treated with 500 μL PBS containing 3x106 UC-MSCs. After MSCs treatment, the rats were sacrificed and the corpus cavernosum tissues were prepared for histological observations.
This study resulted in the administration of UC-MSCs could downregulate the expression of TGF-β, α-SMA, and collagen leading to the improvement of DMED.
UC-MSCs improve the expression of TGF-β, α-SMA, and collagen on erectile dysfunction in streptozotocin-induced diabetic rats.
© 2022 Ade Indra Mukti, Syafruddin Ilyas, Syah Mirsya Warli, Agung Putra, Nur Rasyid, Delfitri Munir, Kamal Basri Siregar, Muhammad Ichwan.

Neuroinflammation within the superficial dorsal horn (SDH) of the spinal cord induces inflammatory pain with symptoms of hyperalgesia and allodynia. Glial activation and production of inflammatory mediators (e.g. cytokines) is associated with modulation of nociceptive signalling. In this context, medicinal signalling cells, e.g. obtained from adipose tissue (AdMSCs), gained attention due to their capacity to modulate the inflammatory response in several diseases, e.g. spinal cord injury. We applied the recently established mixed neuroglial primary cell culture of the rat SDH to investigate effects of AdMSCs on the inflammatory response of SDH cells. Following establishment of a co-cultivation system, we performed specific bioassays for tumour necrosis factor alpha (TNFα) and interleukin (IL)-6, RT-qPCR and immunocytochemistry to detect changes in cytokine production and glial activation upon inflammatory stimulation with lipopolysaccharide (LPS). LPS-induced expression and release of pro-inflammatory cytokines (TNFα, IL-6) by SDH cells was significantly attenuated in the presence of AdMSCs. Further evidence for anti-inflammatory capacities of AdMSCs derived from a blunted LPS-induced TNFα/IL-10 expression ratio and suppressed nuclear translocation of the inflammatory transcription factor nuclear factor kappa B (NFκB) in SDH microglial cells. Expression of IL-10, transforming growth factor beta (TGF-β) and TNFα-stimulated gene-6 (TSG-6) was detected in AdMSCs, which are putative candidates for anti-inflammatory capacities of these cells. We present a novel co-cultivation system of AdMSCs with neuroglial primary cultures of the SDH to investigate immunomodulatory effects of AdMSCs at a cellular level.
© 2021. The Author(s).

Aim To investigate the role of hypoxia-preconditioned mesenchymal stem cells (H-MSCs) in preventing peritoneal adhesion by regulating IL-6 at days 6 and 12. Methods Twenty-four PAs rat model weighing 250 g to 300 g were randomly allocated into 4 groups: sham (Sh), control (C), H-MSCs treatment group at dose 1.5 x 106(T1) and 3 x 106(T2). To induce H-MSCs, all MSCs population were incubated under hypoxia state (5% O2 ), 5% CO2, and 37oC for 24 hours. Expression level of IL-6 was performed using ELISA. Morphological appearance of adhesion was observed by visualizing the existence of adhesion formation in intestinal. Results In this study we found that there was a trend of decrease of IL-6 level on day 6 following MSCs treatments. Interestingly, there was a significant decrease of IL-6 level on day 12 in all treatment groups. Also, no adhesion occurred in T2 group. Conclusions H-MSCs prevent PA development by suppressing the prolonged release of IL-6 at proliferation phase.
Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

h4>Background: /h4> Cell-based therapies with mesenchymal stem cells (MSCs) are considered as promising strategies for spinal cord injury (SCI). MSCs have unique characteristics due to difference in the derived tissues. However, relatively few studies have focused on differences in the therapeutic effects of MSCs derived from different tissues. Here, the therapeutic effects of adipose tissue-derived MSCs (aMSCs), bone marrow-derived MSCs (bMSCs), and cranial bone-derived MSCs (cMSCs) on chronic SCI model rats were compared. Methods MSCs were established from adipose tissue, bone marrow, and cranial bone collected. Neurotrophic factor expression of each MSC type was analyzed by real-time PCR. SCI rats were established with the weight-drop method and transplanted intravenously with MSCs at 4 weeks after SCI. Hind-limb motor function was evaluated from before injury to 4 weeks after transplantation. Endogenous neurotrophic factor and neural repair factor expression in spinal cord (SC) tissue were examined by real-time PCR and western blot analyses. Furthermore, the neurotrophic effects (i.e., neurite formation and elongation) of each MSC type were verified by co-culture with NG108-15 neural cells. Results Although there were no differences in the expression levels of cell surface markers and multipotency, expression of Bdnf , Ngf , and Sort1 ( Nt-3 ) was relatively higher in cMSCs. Transplantation of cMSCs improved motor function of chronic SCI model rats. Although there was no difference in the degree of engraftment of transplanted cells in the injured SC tissue, transplantation of cMSCs enhanced Bdnf , TrkB , and Gap-43 mRNA expression and synaptophysin protein expression in injured SC tissue. In vitro , cMSCs co-cultured with NG108-15 cells promoted neurite formation and elongation. Conclusion As compared with MSCs derived other tissues, cMSCs highly express many neurotrophic factors which improved motor function in chronic SCI model rats by promoting endogenous neurotrophic and neural plasticity factors. These results suggest the efficacy of cMSCs in cell-based therapy for chronic SCI.