Current stem cell research & therapy最新文献

Stem cells hold great promise as novel and encouraging therapeutic tools in the treatment of degenerative disorders due to their differentiation potential while maintaining the capability to self-renewal and their unlimited ability to divide and regenerate tissue. A variety of different types of stem cells can be used in cell therapy. Among these, mesenchymal stem cell (MSC) therapy has gradually established itself as a novel method for treating damaged tissues that need restoration and renewal. Male infertility is an important health challenge affecting approximately 8-12% of people around the world. This abnormality can be caused by primary, congenital, acquired, or idiopathic reasons. Men with no sperm in their semen have a condition called azoospermia, caused by non-obstructive (NOA) causes and post-testicular obstructive causes. Accumulating evidence has shown that various types of MSCs can differentiate into germ cells and improve spermatogenesis in the seminiferous tubules of animal models. In addition, recent studies in animal models have exhibited that extracellular vesicles derived from MSCs can stimulate the progression of spermatogenesis and germ cell regeneration in the recipient testes. In spite of the fact that various improvements have been made in the treatment of azoospermia disorder in animal models by MSC or their extracellular vesicles, no clinical trials have been carried out to test their therapeutic effect on the NOA. In this review, we summarize the potential of MSC transplantation for treating infertility caused by NOA.

Stem cells play a therapeutic role in many diseases by virtue of their strong self-renewal and differentiation abilities, especially in the treatment of autoimmune diseases. At present, the mechanism of the stem cell treatment of autoimmune diseases mainly relies on their immune regulation ability, regulating the number and function of auxiliary cells, anti-inflammatory factors and proinflammatory factors in patients to reduce inflammation. On the other hand, the stem cell- derived secretory body has weak immunogenicity and low molecular weight, can target the site of injury, and can extend the length of its active time in the patient after combining it with the composite material. Therefore, the role of secretory bodies in the stem cell treatment of autoimmune diseases is increasingly important.

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.

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.

Background: A reduced effective local concentration significantly contributes to the unsatisfactory therapeutic results of epirubicin in gastric cancer. Mesenchymal stem cells exhibit targeted chemotaxis towards solid tumors and form tunneling nanotubes with tumor cells, facilitating the delivery of various substances. This study demonstrates the novelty of mesenchymal stem cells in releasing epirubicin into gastric cancer cells through tunneling nanotubes.

Objective: Epirubicin delivery to gastric cancer cells using mesenchymal stem cells.

Methods: In vitro transwell migration assays, live cell tracking, and in vivo targeting assays were used to demonstrate the chemotaxis of mesenchymal stem cells towards gastric cancer. We verified the targeted chemotaxis of mesenchymal stem cells towards gastric cancer cells and the epirubicin loading ability using a high-content imaging system (Equipment type:Operetta CLS). Additionally, tunneling nanotube formation and the targeted release of epirubicin-loaded mesenchymal stem cells co-cultured with gastric cancer cells through mesenchymal stem cell-tunneling nanotubes into gastric cancer cells was observed using Operetta CLS.

Results: Mesenchymal stem cells demonstrated targeted chemotaxis towards gastric cancer, with effective epirubicin loading and tolerance. Co-culturing induced tunneling nanotube formation between these cells. Epirubicin-loaded mesenchymal stem cells were released into gastric cancer cells through tunneling nanotubes, significantly increasing their non-viability compared to the negative control group (p < 0.05).

Conclusions: We identified a novel approach for precisely targeting epirubicin release in gastric cancer cells. Therefore, mesenchymal stem cell-tunneling nanotubes could serve as a potential tool for targeted delivery of drugs, enhancing their chemotherapeutic effects in cancer cells.

Background: Aging is a biological and gradual deterioration of function in living organisms. Aging is one of the risk factors for heart disease.

Objective: Although mesenchymal stem cell transplantation shows potential in heart disease treatment, the relationship between stem cell-based therapy and oxidative stress/inflammasome axis regulation remains unclear. This study hypothesized that intervention of stem cells showed protective effect on heart aging induced by D-galactose through regulation of oxidative stress/inflammasome axis.

Methods: An aging animal model was designed to test the above hypothesis. Experimental animals were divided into three groups, including Sham, D-gal (aging rats induced by d-galactose), and D-gal+WJSC (aging rats receiving mesenchymal stem cells).

Results: Compared to the Sham, the experimental results indicate that structural alteration (HE stain and Masson's Trichrome stain), oxidative stress elevation (increase of TBARS level, expression of gp-91 and suppression of Sirt-1 as well as SOD2), increase of aging marker p53, suppression of cardiogenesis marker Troponin T, and inflammasome related protein markers expression (NLRP3, caspase-1 and IL-1 beta) were significantly observed in D-gal. In contrast, all pathological pathways were significantly improved in D-gal+WJSC when compared to D-gal. In addition, migration of stem cells to aging heart tissues was observed in the D-gal+WJSC group.

Conclusion: These findings suggest that mesenchymal stem cell transplantation effectively ameliorates aging hearts through oxidative stress/inflammasome axis regulation. The results from this study provide clinical potential for stem cell-based therapy in the treatment of aging hearts.

Mice with severe immunodeficiencies have become very important tools for studying foreign cells in an in vivo environment. Xenotransplants can be used to model cells from many species, although most often, mice are humanized through the transplantation of human cells or tissues to meet the needs of medical research. The development of immunodeficient mice is reviewed leading up to the current state-of-the-art strains, such as the NOD-scid-gamma (NSG) mouse. NSG mice are excellent hosts for human hematopoietic stem cell transplants or immune reconstitution through transfusion of human peripheral blood mononuclear cells. However, barriers to full hematopoietic engraftment still remain; notably, the survival of human cells in the circulation is brief, which limits overall hematological and immune reconstitution. Reports have indicated a critical role for monocytic cells - monocytes, macrophages, and dendritic cells - in the clearance of xenogeneic cells from circulation. Various aspects of the NOD genetic background that affect monocytic cell growth, maturation, and function that are favorable to human cell transplantation are discussed. Important receptors, such as SIRPα, that form a part of the innate immune system and enable the recognition and phagocytosis of foreign cells by monocytic cells are reviewed. The development of humanized mouse models has taken decades of work in creating more immunodeficient mice, genetic modification of these mice to express human genes, and refinement of transplant techniques to optimize engraftment. Future advances may focus on the monocytic cells of the host to find ways for further engraftment and survival of xenogeneic cells.

Type 1 Diabetes (T1D) is characterized by hyperglycemia, and caused by a lack of insulin secretion. At present there is no cure for T1D and patients are dependent on exogenous insulin for lifelong, which seriously affects their lives. Mesenchymal stem cells (MSCs) can be differentiated to β cell-like cells to rescue the secretion of insulin and reconstruct immunotolerance to preserve the function of islet β cells. Due to the higher proportion of children and adolescents in T1D patients, the efficacy and safety issue of the application of MSC's transplant in T1D was primarily demonstrated and identified by human clinical trials in this review. Then we clarified the mechanism of MSCs to relieve the symptom of T1D and found out that UC-MSCs have no obvious advantage over the other types of MSCs, the autologous MSCs from BM or menstrual blood with less expanded ex vivo could be the better choice for clinical application to treat with T1D through documentary analysis. Finally, we summarized the advances of MSCs with different interventions such as genetic engineering in the treatment of T1D, and demonstrated the advantages and shortage of MSCs intervened by different treatments in the transplantation, which may enhance the clinical efficacy and overcome the shortcomings in the application of MSCs to T1D in future.

Objective: In recent times, it has been recognized that mesenchymal stem cells (MSCs) possess the capability to address osteoarthritis (OA). The objective of this research was to examine the impact of injecting human adipose-derived stem cells (hADSCs) into a novel rabbit osteoarthritis model with dual damage.

Methods: The OA model was established surgically first by medial collateral ligament and anterior cruciate ligament transection and medial meniscectomy, then by articular cartilage full-thickness defect. Enhanced Green Fluorescence Protein expressing lentivirus FG12 was used to label hADSCs, which were then injected into the knee joints. Every single rabbit was sacrificed after 4 and 8 weeks following the surgical procedure. Macroscopic examination, immunohistochemistry staining, magnetic resonance imaging, qRT-PCR, and ELISA analysis were utilized for the assessments.

Results: After 4 and 8 weeks, the injection of hADSCs resulted in reduced cartilage loss, minimal fissures and cracks, and a decrease in the volume of joint effusion and cartilage defect as measured by MRI. Moreover, the application of ELISA and qRT-PCR techniques revealed that the administration of hADSCs resulted in an elevation in the IGF-1 concentration.

Conclusions: Based on our findings, it can be inferred that the transplantation of hADSCs facilitates the healing of articular cartilage in the osteoarthritis model of rabbits with double damage. The upregulated IGF-1 may play a crucial part in the process of cartilage repair using hADSCs. The use of hADSC transplantation could potentially be appropriate for clinical implementation in managing osteoarthritis.

Background: MSCs are a part of the tumor microenvironment, which secrete cytokines and chemokines. They can affect metastasis and the growth of tumors. metastamiRs are newly recognized regulatory elements of the metastasis pathway which are involved in epithelial-to-mesenchymal transition (EMT).

Objective: In the present study, we aimed to assess the expression profile of metastamiRs in the context of MSCs in correlation with their invasion and migration power.

Methods: Tumor-isolated BC-MSCs and normal human mammary epithelial cells (HMECs) along with MCF-7, MDA-MB231, and MCF-10A cells were prepared and confirmed for their identity. The cells were assessed for CD44+CD24¯ percentage, Oct-4, and Survivin expression. GEO, KEGG, and TCGA databases were investigated to detect differential miR-expressions. Real- time PCR for 13 miRs was performed using LNA primers. Ultimately, Transwell-Matrigel assays as used to assess the level of migration and invasion.

Results: Our results indicated that some oncomiRs like miR-10b were upregulated in BC-MSCs, while the levels of miR-373 and miR-520c were similar to the MCF-10A. Generally, miR-200 family members were on lower levels compared to the other miR-suppressor (miR-146a, 146b, and 335). miR-31 and 193b were up-regulated in MCF-10A. The most invasiveness was observed in the MDA-MB231 cell line.

Conclusion: We have demonstrated that the miR-expression levels of BC-MSCs are somewhat in between MCF-7 and MDA-MB231 miR-expression levels. This could be the logic behind the moderate level of invasion in BC-MSCs. Therefore, miR-therapy approaches such as miR-mimic or antagomiRs could be used for BC-MSCs in clinical cancer therapy.