Current Stem Cell Research & Therapy - Volume 19, Issue 8, 2024

Mesenchymal Stem Cells (MSCs) are being investigated as a treatment for a novel viral disease owing to their immunomodulatory, anti-inflammatory, tissue repair and regeneration characteristics, however, the exact processes are unknown. MSC therapy was found to be effective in lowering immune system overactivation and increasing endogenous healing after SARS-CoV-2 infection by improving the pulmonary microenvironment. Many studies on mesenchymal stem cells have been undertaken concurrently, and we may help speed up the effectiveness of these studies by collecting and statistically analyzing data from them. Based on clinical trial information found on clinicaltrials. gov and on 16 November 2020, which includes 63 clinical trials in the field of patient treatment with COVID-19 using MSCs, according to the trend of increasing studies in this field, and with the help of meta-analysis studies, it is possible to hope that the promise of MSCs will one day be realized. The potential therapeutic applications of MSCs for COVID-19 are investigated in this study.

This comprehensive review article examines the integration of biotechnology and stem cell therapy in breast cancer diagnosis and treatment. It discusses the use of biotechnological tools such as liquid biopsies, genomic profiling, and imaging technologies for accurate diagnosis and monitoring of treatment response. Stem cell-based approaches, their role in modeling breast cancer progression, and their potential for breast reconstruction post-mastectomy are explored. The review highlights the importance of personalized treatment strategies that combine biotechnological tools and stem cell therapies. Ethical considerations, challenges in clinical translation, and regulatory frameworks are also addressed. The article concludes by emphasizing the potential of integrating biotechnology and stem cell therapy to improve breast cancer outcomes, highlighting the need for continued research and collaboration in this field.

Wound infection often requires a long period of care and an onerous treatment process. Also, the rich environment makes the wound an ideal niche for microbial growth. Stable structures, like biofilm, and drug-resistant strains cause a delay in the healing process, which has become one of the important challenges in wound treatment. Many studies have focused on alternative methods to deal the wound infections. One of the novel and highly potential ways is mesenchymal stromal cells (MSCs). MSCs are mesoderm-derived pluripotent adult stem cells with the capacity for self-renewal, multidirectional differentiation, and immunological control. Also, MSCs have anti-inflammatory and antiapoptotic effects. MScs, as pluripotent stromal cells, differentiate into many mature cells. Also, MSCs produce antimicrobial compounds, such as antimicrobial peptides (AMP), as well as secrete immune modulators, which are two basic features considered in wound healing. Despite the advantages, preserving the structure and activity of MSCs is considered one of the most important points in the treatment. MSCs’ antimicrobial effects on microorganisms involved in wound infection have been confirmed in various studies. In this review, we aimed to discuss the antimicrobial and therapeutic applications of MSCs in the infected wound healing processes.

The theory of cancer stem cells is a breakthrough discovery that offers exciting possibilities for comprehending the biological behavior of tumors. More and more evidence suggests that retinoblastoma cancer stem cells promote tumor growth and are likely to be the origin of tumor formation, drug resistance, recurrence, and metastasis. At present, some progress has been made in the verification, biological behavior, and drug resistance mechanism of retinoblastoma cancer stem cells. This article aims to review the relevant research and explore future development direction.

Background: Several types of stem cells are available for the treatment of stroke patients. However, the optimal type of stem cell remains unclear. Objective: To analyze the effects of bone marrow-derived stem cell therapy in patients with ischemic stroke by integrating all available direct and indirect evidence in network meta-analyses. Methods: We searched several databases to identify randomized clinical trials comparing clinical outcomes of bone marrow-derived stem cell therapy vs. conventional treatment in stroke patients. Pooled relative risks (RRs) and mean differences (MDs) were reported. The surface under the cumulative ranking (SUCRA) was used to rank the probabilities of each agent regarding different outcomes. Results: Overall, 11 trials with 576 patients were eligible for analysis. Three different therapies, including mesenchymal stem cells (MSCs), mononuclear stem cells (MNCs), and multipotent adult progenitor cells (MAPCs), were assessed. The direct analysis demonstrated that stem cell therapy was associated with significantly reduced all-cause mortality rates (RR 0.55, 95% CI 0.33 to 0.93; I²=0%). Network analysis demonstrated MSCs ranked first in reducing mortality (RR 0.42, 95% CrI 0.15 to 0.86) and improving modified Rankin Scale score (MD -0.59 95% CI -1.09 to -0.09), with SUCRA values 80%, and 98%, respectively. Subgroup analysis showed intravenous transplantation was superior to conventional therapy in reducing all-cause mortality (RR 0.53, 95% CrI 0.29 to 0.88). Conclusion: Using stem cell transplantation was associated with reduced risk of death and improved functional outcomes in patients with ischemic stroke. Additional large trials are warranted to provide more conclusive evidence.

Background: The unique potential of stem cells to restore vision and regenerate damaged ocular cells has led to the increased attraction of researchers and ophthalmologists to ocular regenerative medicine in recent decades. In addition, advantages such as easy access to ocular tissues, non-invasive follow-up, and ocular immunologic privilege have enhanced the desire to develop ocular regenerative medicine. Objective: This study aimed to characterize central and nasal orbital adipose stem cells (OASCs) and their neural differentiation potential. Methods: The central and nasal orbital adipose tissues extracted during an upper blepharoplasty surgery were explant-cultured in Dulbecco’s Modified Eagle Medium (DMEM)/F12 supplemented with 10% fetal bovine serum (FBS). Cells from passage 3 were characterized morphologically by osteogenic and adipogenic differentiation potential and by flow cytometry for expression of mesenchymal (CD73, CD90, and CD105) and hematopoietic (CD34 and CD45) markers. The potential of OASCs for the expression of NGF, PI3K, and MAPK and to induce neurogenesis was assessed by real-time PCR. Results: OASCs were spindle-shaped and positive for adipogenic and osteogenic induction. They were also positive for mesenchymal and negative for hematopoietic markers. They were positive for NGF expression in the absence of any significant alteration in the expression of PI3K and MAPK genes. Nasal OASCs had higher expression of CD90, higher potential for adipogenesis, a higher level of NGF expression under serum-free supplementation, and more potential for neuron-like morphology. Conclusion: We suggested the explant method of culture as an easy and suitable method for the expansion of OASCs. Our findings denote mesenchymal properties of both central and nasal OASCs, while mesenchymal and neural characteristics were expressed stronger in nasal OASCs when compared to central ones. These findings can be added to the literature when cell transplantation is targeted in the treatment of neuro-retinal degenerative disorders.

Background and Objectives: Orthodontic treatment involves the application of mechanical force to induce periodontal tissue remodeling and ultimately promote tooth movement. It is essential to study the response mechanisms of human periodontal ligament stem cells (hPDLSCs) to improve orthodontic treatment. Methods: In this study, hPDLSCs treated with compressive force were used to simulate orthodontic treatment. Cell viability and cell death were assessed using the CCK-8 assay and TUNEL staining. Alkaline phosphatase (ALP) and alizarin red staining were performed to evaluate osteogenic differentiation. The binding relationship between IGF1 and METTL14 was assessed using RIP and dual-luciferase reporter assays. Results: The compressive force treatment promoted the viability and osteogenic differentiation of hPDLSCs. Additionally, m6A and METTL14 levels in hPDLSCs increased after compressive force treatment, whereas METTL14 knockdown decreased cell viability and inhibited the osteogenic differentiation of hPDLSCs treated with compressive force. Furthermore, the upregulation of METTL14 increased m6A levels, mRNA stability, and IGF1 expression. RIP and dual-luciferase reporter assays confirmed the interaction between METTL14 and IGF1. Furthermore, rescue experiments demonstrated that IGF1 overexpression reversed the effects of METTL14 knockdown in hPDLSCs treated with compressive force. Conclusions: In conclusion, this study demonstrated that compressive force promotes cell viability and osteogenic differentiation of hPDLSCs by regulating IGF1 levels mediated by METTL14.

Background: Diabetic peripheral neuropathy causes significant pain to patients. Umbilical cord mesenchymal stem cells have been shown to be useful in the treatment of diabetes and its complications. The aim of this study was to investigate whether human umbilical cord mesenchymal stem cells treated with interferon-gamma can ameliorate nerve injury associated with diabetes better than human umbilical cord mesenchymal stem cells without interferon-gamma treatment. Methods: Human umbilical cord mesenchymal stem cells were assessed for adipogenic differentiation, osteogenic differentiation, and proliferation ability. Vonfry and a hot disc pain tester were used to evaluate tactile sensation and thermal pain sensation in mice. Hematoxylin-eosin and TUNEL staining were performed to visualize sciatic nerve fiber lesions and Schwann cell apoptosis in diabetic mice. Western blotting was used to detect expression of the apoptosis-related proteins Bax, B-cell lymphoma-2, and caspase-3 in mouse sciatic nerve fibers and Schwann cells. Real-Time Quantitative PCR was used to detect mRNA levels of the C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 2, C-X-C motif chemokine ligand 9, and C-X-C motif chemokine ligand 10 in mouse sciatic nerve fibers and Schwann cells. Enzyme-linked immunosorbent assay was used to detect levels of the inflammatory cytokines, interleukin- 1β, interleukin-6, and tumor necrosis factor-α in serum and Schwann cells. Results: The adipogenic differentiation capacity, osteogenic differentiation capacity, and proliferation ability of human umbilical cord mesenchymal stem cells were enhanced after interferon-gamma treatment. Real-Time Quantitative PCR revealed that interferon-gamma promoted expression of the adipogenic markers, PPAR-γ and CEBP-α, as well as of the osteogenic markers secreted phosphoprotein 1, bone gamma-carboxyglutamate protein, collagen type I alpha1 chain, and Runt-related transcription factor 2. The results of hematoxylin-eosin and TUNEL staining showed that pathological nerve fiber damage and Schwann cell apoptosis were reduced after the injection of interferon-gamma-treated human umbilical cord mesenchymal stem cells. Expression of the apoptosis-related proteins, caspase-3 and Bax, was significantly reduced, while expression of the anti-apoptotic protein B-cell lymphoma-2 was significantly increased. mRNA levels of the cell chemokines, C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 2, C-X-C motif chemokine ligand 9, and C-X-C motif chemokine ligand 10, were significantly reduced, and levels of the inflammatory cytokines, interleukin-1β, interleukin-6, and tumor necrosis factor-α, were decreased. Tactile and thermal pain sensations were improved in diabetic mice. Conclusion: Interferon-gamma treatment of umbilical cord mesenchymal stem cells enhanced osteogenic differentiation, adipogenic differentiation, and proliferative potential. It can enhance the ability of human umbilical cord mesenchymal stem cells to alleviate damage to diabetic nerve fibers and Schwann cells, in addition to improving the neurological function of diabetic mice.

Background: Transplantation of stem cells/scaffold is an efficient approach for treating tissue injury including full-thickness skin defects. However, the application of stem cells is limited by preservation issues, ethical restriction, low viability, and immune rejection in vivo. The mesenchymal stem cell conditioned medium is abundant in bioactive functional factors, making it a viable alternative to living cells in regeneration medicine. Methods: Nasal mucosa-derived ecto-mesenchymal stem cells (EMSCs) of rats were identified and grown in suspension sphere-forming 3D culture. The EMSCs-conditioned medium (EMSCs-CM) was collected, lyophilized, and analyzed for its bioactive components. Next, fibrinogen and chitosan were further mixed and cross-linked with the lyophilized powder to obtain functional skin patches. Their capacity to gradually release bioactive substances and biocompatibility with epidermal cells were assessed in vitro. Finally, a full-thickness skin defect model was established to evaluate the therapeutic efficacy of the skin patch. Results: The EMSCs-CM contains abundant bioactive proteins including VEGF, KGF, EGF, bFGF, SHH, IL-10, and fibronectin. The bioactive functional composite skin patch containing EMSCs-CM lyophilized powder showed the network-like microstructure could continuously release the bioactive proteins, and possessed ideal biocompatibility with rat epidermal cells in vitro. Transplantation of the composite skin patch could expedite the healing of the full-thickness skin defect by promoting endogenous epidermal stem cell proliferation and skin appendage regeneration in rats. Conclusion: In summary, the bioactive functional composite skin patch containing EMSCs-CM lyophilized powder can effectively accelerate skin repair, which has promising application prospects in the treatment of skin defects.

Background: Angiogenesis and energy metabolism mediated by adipose mesenchymal stem cell-derived exosomes (AMSC-exos) are promising therapeutics for vascular diseases. Objectives: The current study aimed to explore whether AMSC-exos have therapeutic effects on oxygen and glucose deprivation (OGD) human umbilical vein endothelial cells (HUVECs) injury by modulating the SIX1/HBO1 signaling pathway to upregulate endothelial cells (E.C.s) glycolysis and angiogenesis. Methods: AMSC-exos were isolated and characterized following standard protocols. AMSC-exos cytoprotective effects were evaluated in the HUVECs-OGD model. The proliferation, migration, and tube formation abilities of HUVECs were assessed. The glycolysis level was evaluated by detecting lactate production and ATP synthesis. The expressions of HK2, PKM2, VEGF, HIF-1α, SIX1, and HBO1 were determined by western blotting, and finally, the SIX1 overexpression vector or small interfering RNA (siRNA) was transfected into HUVECs to assess the change in HBO1 expression. Results: Our study revealed that AMSC-exos promotes E.C.s survival after OGD, reducing E.C.s apoptosis while strengthening E.C.'s angiogenic ability. AMSC-exos enhanced glycolysis and reduced OGD-induced ECs injury by modulation of the SIX1/HBO1 signaling pathway, which is a novel anti-endothelial cell injury role of AMSC-exos that regulates glycolysis via activating the SIX1/HBO1 signaling pathway. Conclusion: The current study findings demonstrate a useful angiogenic therapeutic strategy for AMSC-exos treatment in vascular injury, thus providing new therapeutic ideas for treating ischaemic diseases.

Background: Stem cell-released exosomes (EXs) have shown beneficial effects on regenerative diseases. Our previous study has revealed that EXs of endothelial progenitor cells (EPC-EXs) can elicit favorable effects on endothelial function. EXs may vary greatly in size, composition, and cargo uptake rate depending on the origins and stimulus; notably, EXs are promising vehicles for delivering microRNAs (miRs). Since miR-210 is known to protect cerebral endothelial cell mitochondria by reducing oxidative stress, here we study the effects of miR-210-loaded EPC-EXs (miR210-EPC-EXs) on ischemic brain damage in acute ischemic stroke (IS). Methods: The miR210-EPC-EXs were generated from EPCs transfected with miR-210 mimic. Middle cerebral artery occlusion (MCAO) surgery was performed to induce acute IS in C57BL/6 mice. EPC-EXs or miR210-EPC-EXs were administrated via tail vein injection 2 hrs after IS. To explore the potential mechanisms, inhibitors of the vascular endothelial growth factor receptor 2 (VEGFR2)/PI3 kinase (PI3K) or tyrosine receptor kinase B (TrkB)/PI3k pathways were used. The brain tissue was collected after treatments for infarct size, cell apoptosis, oxidative stress, and protein expression (VEGFR2, TrkB) analyses on day two. The neurological deficit score (NDS) was evaluated before collecting the samples. Results: 1) As compared to EPC-EXs, miR210-EPC-EXs profoundly reduced the infarct volume and improved the NDS on day two post-IS. 2) Fewer apoptosis cells were detected in the peri-infarct brain of mice treated with miR210-EPC-EXs than in EPC-EXs-treated mice. Meanwhile, the oxidative stress was profoundly reduced by miR210-EPC-EXs. 3) The ratios of p-PI3k/PI3k, p- VEGFR2/VEGFR2, and p-TrkB/TrkB in the ipsilateral brain were raised by miR210-EPC-EXs treatment. These effects could be significantly blocked or partially inhibited by PI3k, VEGFR2, or TrkB pathway inhibitors. Conclusion: These findings suggest that miR210-EPC-EXs protect the brain from acute ischemia- induced cell apoptosis and oxidative stress partially through the VEGFR2/PI3k and TrkB/PI3k signal pathways.