Vol 19, No 9 (2024)

Medicine

Mesenchymal Stem Cell Transplantation in Type 1 Diabetes Treatment: Current Advances and Future Opportunity

Liu J., Wan X., Zheng S., Khan M., He H., Feng Y., Xiao J., Chen Y., Hu X., Zhang Q., Xiong K.

Abstract

: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.

Current Stem Cell Research & Therapy. 2024;19(9):1175-1184
pages 1175-1184 views

Cancer Stem Cells in Carcinogenesis and Potential Role in Pancreatic Cancer

Sharma R., Malviya R.

Abstract

:A poor prognosis is associated with pancreatic cancer because of resistance during treatment and early distant metastases. The discovery of cancer stem cells has opened up novel avenues for research into the biology and treatment of cancer. Many investigations have pointed out the role of these types of stem cells in the oncogenesis and progression of hematologic and solid malignancies, specifically. Due to the existence of cancer stem cells in the proliferation and preservation of pancreatic tumors, such malignancies could be difficult to eradicate using conventional treatment techniques like chemotherapy and radiotherapy. It is hypothesized that pancreatic malignancies originate from a limited population of aberrant cancer stem cells to promote carcinogenesis, tumour metastasis, and therapeutic resistance. This review examines the role of pancreatic cancer stem cells in this disease and their significance in carcinogenesis, as well as the signals which modulate them, and also examines the ongoing clinical studies that are now being conducted with pancreatic stem cells.

Current Stem Cell Research & Therapy. 2024;19(9):1185-1194
pages 1185-1194 views

Potential Druggability of Mesenchymal Stem/Stromal Cell-derived Exosomes

Zhang F., Zhang L., Yu H.

Abstract

:Exosomes secreted by mesenchymal stem/stromal cells (MSC-Exos) are advantageous candidate sources for novel acellular therapy. Despite the current standards of good manufacturing practice (GMP), the deficiency of suitable quality-control methods and the difficulties in large-scale preparation largely restrict the development of therapeutic products and their clinical applications worldwide. Herein, we mainly focus on three dominating issues commonly encountered in exosomal GMP, including issues upstream of the cell culture process, downstream of the purification process, exosomes quality control, and the drug properties of exosomes and their druggability from a corporate perspective. Collectively, in this review article, we put forward the issues of preparing clinical exosome drugs for the treatment of diverse diseases and provide new references for the clinical application of GMP-grade MSC-Exos.

Current Stem Cell Research & Therapy. 2024;19(9):1195-1209
pages 1195-1209 views

Tumor Organoid as a Drug Screening Platform for Cancer Research

Arani R., Yousefi N., Hamidieh A., Gholizadeh F., Sisakht M.

Abstract

:A number of studies have been conducted on the application of 3D models for drug discovery, drug sensitivity assessment, and drug toxicity. Most of these studies focused on disease modelling and attempted to control cellular differentiation, heterogeneity, and key physiological features to mimic organ reconstitution so that researchers could achieve an accurate response in drug evaluation. Recently, organoids have been used by various scientists due to their highly organotypic structure, which facilitates the translation from basic research to the clinic, especially in cancer research. With this tool, researchers can perform high-throughput analyses of compounds and determine the exact effect on patients based on their genetic variations, as well as develop personalized and combination therapies. Although there is a lack of standardization in organoid culture, patientderived organoids (PDOs) have become widely established and used for drug testing. In this review, we have discussed recent advances in the application of organoids and tumoroids not only in cancer research for drug screening but also in clinical trials to demonstrate the potential of organoids in translational medicine.

Current Stem Cell Research & Therapy. 2024;19(9):1210-1250
pages 1210-1250 views

Generating Retinas through Guided Pluripotent Stem Cell Differentiation and Direct Somatic Cell Reprogramming

Zhang K., Cai W., Hu L., Chen S.

Abstract

:Retinal degeneration diseases affect millions of people worldwide but are among the most difficult eye diseases to cure. Studying the mechanisms and developing new therapies for these blinding diseases requires researchers to have access to many retinal cells. In recent years there has been substantial advances in the field of biotechnology in generating retinal cells and even tissues in vitro, either through programmed sequential stem cell differentiation or direct somatic cell lineage reprogramming. The resemblance of these in vitro-generated retinal cells to native cells has been increasingly utilized by researchers. With the help of these in vitro retinal models, we now have a better understanding of human retinas and retinal diseases. Furthermore, these in vitro-generated retinal cells can be used as donor cells which solves a major hurdle in the development of cell replacement therapy for retinal degeneration diseases, while providing a promising option for patients suffering from these diseases. In this review, we summarize the development of pluripotent stem cell-to-retinal cell differentiation methods, the recent advances in generating retinal cells through direct somatic cell reprogramming, and the translational applications of retinal cells generated in vitro. Finally, we discuss the limitations of the current protocols and possible future directions for improvement.

Current Stem Cell Research & Therapy. 2024;19(9):1251-1262
pages 1251-1262 views

Transient Fever: The Sole Treatment-Related Adverse Event Associated with Mesenchymal Stromal Cells and Solid Clues from the Real World

Wang Y., Mou Q., Yi H., Meng Z.

Abstract

Background:The number of trials investigating mesenchymal stromal cells (MSCs) soars within 3 years which urges a study analysing emerging MSC treatment-related adverse events.

Aim:To assess the safety of MSC therapy and provide solid evidence for clinical translation of MSC.

Methods:A meta-analysis of randomized clinical trials (RCTs) published up to April 20th, 2023 was performed. Odds ratio (OR) and 95% confidential intervals (CIs) were used to display pooled results.

Results:152 randomized clinical trials (RCTs) that incorporated 9228 individuals treated with MSCs from autologous or allogenic adipose tissue, bone marrow, Wharton's Jelly, and placenta tissue were included in the analysis. We discovered appropriate 21 MSC treatment-related adverse events (TRAEs), of which fever [OR, 1.61, 95% CI: 1.22-2.11, p(<0.01] was the sole event that was closely associated with MSC therapy. MSCs also trended to lower the incidence rate of tachycardia [OR, 0.83, 95% CI: 0.64-1.09, p=0.14] and fatigue [OR, 0.18, 95% CI: 0.61-1.07, p=0.18]. A separate analysis of studies with long-term follow-up (more than 1 year) demonstrated the close relationship between MSCs and fever [OR, 1.75, 95% CI: 1.26-2.24, p(<0.01]. The rest TRAEs did not associate themselves with MSC therapy. Dose-response was also conducted for fever, linearity was discovered between MSCs from allogeneic tissue and Wharton's Jelly and fever.

Conclusion:To date, our results suggest that fever is the only AE closely associated with MSCs.

Current Stem Cell Research & Therapy. 2024;19(9):1263-1285
pages 1263-1285 views

In-vitro Augmentation of Mesenchymal Stem Cells by Using Adult Bovine Serum

Shehzadi S., Javed M., Ullah A., Bilal Waqar A., Iftikhar Shah F., Ullah S.

Abstract

Background:Umbilical cord mesenchymal stem cells (UC-MSCs) are increasingly being utilized for immune-related disease therapies due to their low immunogenicity. However, the primary culture of UC-MSCs requires the supplementation of serum in the growth medium, which has posed a challenge due to ethical issues related to the collection method of the fetal bovine serum (FBS) that is routinely used in cell culture.

Aim:In order to address this, the purpose of this research was to assess the effectiveness of adult bovine serum (ABS) as a different and more affordable source of serum for the in-vitro cultivation of UC-MSCs. UC-MSCs were isolated from the umbilical cord of Wharton’s jelly of cow immediately after birth, by digestion with Collagenase type I.

Method:ABS was collected from fresh bovine sources and heat-inactivated. The morphology of UC-MSCs was observed under an inverted microscope, and growth patterns, proliferative index, and doubling time were calculated every two days to compare the efficacy of ABS with FBS. Immunocytochemistry for specific markers was also conducted on the MSCs.

Result:The results showed a notable difference in morphology, growth rate, population doubling, and proliferative index between ABS and FBS.

Conclusion:Intriguingly, ABS proved to be an effective supplement in the growth medium for expanding UC-MSCs in vitro, providing a viable alternative to FBS.

Current Stem Cell Research & Therapy. 2024;19(9):1286-1292
pages 1286-1292 views