Current Stem Cell Research & Therapy - Volume 18, Issue 3, 2023

Background: Over the past few years, mesenchymal stem cells (MSCs) have been regarded as effective for treating various diseases. Among the types of MSCs, human umbilical cord mesenchymal stem cells (hUC-MSCs) have been widely studied because of their advantages in non-invasive damage to donors and the wide range of sources. Main body: This article reviews three aspects of hUC-MSCs. Foremost are the latest advances in the cultivation and preparation methods of hUC-MSCs. Furthermore, the treatments mechanism of hUCMSCs in organ transplantation and liver diseases. Finally, a summary of their use in clinical trials in liver diseases. The first part of this paper emphasizes the differences between the selection area and culture factors, including the separation method, long-term culturing in vitro, medium composition, serum, and three-dimensional (3D) skeleton system training, which could affect the characteristics of hUC-MSCs and the treatment of diseases. The second section mainly stresses the mechanisms of hUC-MSCs in the treatment of diseases, including immunoregulation and transdifferentiation into hepatocyte-like cells. Many new technologies mark and track cells in vivo and their safety. Briefly mention its role in the treatment of other diseases and vaccine preparation. In the third part, to accelerate the application of hUC-MSCs in the treatment of clinical diseases, it is necessary to expand the sample size of clinical trials to ensure their safety in the human body and determine the most effective infusion method and volume. Conclusion: hUC-MSCs have a substantial potential to become a more effective treatment for liver diseases. Clinical trials and mechanisms have laid the foundation for the normalization of clinical hUC-MSCs delivery.

Mesenchymal stem cells (MSCs) are self-renewing cells found in almost all postnatal organs and tissues in the perivascular region. These cells have a high capacity for mesodermal differentiation; however, numerous studies have shown that MSCs can also differentiate into cells of endodermal and ectodermal lineages. Due to this multilineage differentiation capacity, these cells could function as restoratives of various cell populations after transplantation. However, not only their differentiation potential makes them ideal candidates for this, but also a series of trophic properties that promote regeneration in the surrounding tissue, such as their migratory capacity, secretory and immunomodulatory actions. This review analyzes several MSC transplantation trials to treat neurological diseases, such as demyelinating injury, spinal cord injury, paraplegia, Parkinson's disease, cochlear injury, and Alzheimer's disease. These cells could facilitate functional recovery in multiple models of neurodegenerative diseases and nervous system injuries by using their trophic capacities, reducing inflammation in the injured area, reducing apoptosis, and enhancing endogenous neurogenesis through the secretion of bioactive factors. Furthermore, since cells derived from patients have demonstrated disease-associated differences in various brain diseases, these cells represent an excellent candidate for the study of these diseases, functioning as "a window to the brain."

Infertility in women can be caused by various female reproductive diseases such as premature ovarian failure (POF), polycystic ovary syndrome (PCOS), endometriosis and Asherman syndrome that affect couples' quality of life and lead to mental, emotional, and physical problems. In recent years, clinical researchers have sought infertility treatments using new methods that are more effective and noninvasive than the old methods. Today, stem cell-based therapy has been introduced as a promising method and an alternative to the old strategy of infertility treatment. Understanding the main features and functional perspective of mesenchymal stem cells (MSCs) in the future of infertility by physicians is crucial. Mesenchymal stem cells (MSCs) are multipotent stem cells with a high proliferation range, abundant source and multidirectional differentiation potential. They have a high potential for the treatment of injured tissues in regenerative medicine through cell homing, secretion of active factors, and participation in immune regulation. At present, due to fewer ethical restrictions on the use of mesenchymal stem cells compared to embryonic stem cells, more attention has been paid to these cells as a new treatment for gynecological disorders. In this paper, we first review the various type of female reproductive disorders along with their common treatment methods, then we evaluate the recent advances in the application of MSCs in the diseases related to infertility and improve the reproductive health of women worldwide.

Osteoporosis is a systemic disease in which bone mass decreases, leading to an increased risk of bone fragility and fracture. The occurrence of osteoporosis is believed to be related to the disruption of the differentiation of mesenchymal stem cells into osteoblasts and adipocytes. N6-adenylate methylation (m6A) modification is the most common type of chemical RNA modification and refers to a methylation modification formed by the nitrogen atom at position 6 of adenine (A), which is catalyzed by a methyltransferase. The main roles of m6A are the post-transcriptional level regulation of the stability, localization, transportation, splicing, and translation of RNA; these are key elements of various biological activities, including osteoporosis and the differentiation of mesenchymal stem cells into osteoblasts and adipocytes. The main focus of this review is the role of m6A in these two biological processes.

Adipose-derived stem cells (ADSCs) have been described as one of the most potent and accessible human adult stem cells which can be utilized in various therapeutic approaches. Due to the wide variety of cytokines and GFs secreted by them, ADSCs can be used for controlled drug release. These cells can be used for proliferation and differentiation of tissues regardless of survival conditions and immunologic problems. Because of their ability to differentiate into various lineages, ADSCs can be used in musculoskeletal problems, diabetes, heart diseases, obesity, neurologic and nephrogenic diseases, and wound healing, as well as applications in regenerative medicine such as osteogenic, cartilage, tendon, muscle, skin, CNS, cardiac and vascularization, as well as liver and even periodontal regeneration. To maintain the highest viability and efficiency, companies that provide ADSCs should offer the best product quality to gain market share and scientists need to acquire an understanding of sources where they can find the best products available. Therefore, in this article, we have reviewed the available products, companies and the market size currently available for ADSCs. Enormous effort has been made to list the most important trials, products and companies currently existent in the field. To achieve better outcomes in scientific research, there is the need to compare the products available and choose the best option according to desired goals. Thus, this paper provides a valuable reference for those interested in the field of ADSCs and their applications.

Background: Neural stem/progenitor cells (NSPCs) transplantation has been recognized in recent years as an effective strategy for the treatment of ischemic stroke. Several preclinical studies have demonstrated the feasibility, safety, and efficacy of NSPCs therapy. Methods: We conducted a systematic review of the published literature in Pubmed reporting the use of NSPCs in preclinical studies between 2010 and 2021. Based on the articles reporting data, the key factors affecting efficacy were listed. Results: A total of 71 preclinical studies, including 91 treatment arms, were identified. The results showed that several factors could influence the outcomes of NSPCs transplantation, including the type of donor cells, cell dose, time of administration after stroke, delivery route, and anesthetic. Treatment outcomes were measured by infarct volume, behavioral tests, and molecular and cellular level results. Conclusion: Most of the preclinical studies reported statistically significant effects and very few adverse reactions. Transplantation of NSPCs for ischemic stroke still needs to be optimized for several key factors. A standardized treatment outcome assessment could ease the translation of evidence in clinical settings.

Objective: The aim of the study was to reveal the changes in serum protein composition and content in macaques during the process of ageing, and explore the effect of bone marrow mesenchymal stem cell (BMMSC) on the serum protein expression profile in elderly macaques. Methods: Naturally ageing macaques were assessed according to age. BMMSCs were intravenously infused into aged macaques. In addition, peripheral blood was collected to obtain serum for dataindependent acquisition (DIA) protein sequencing to identify aging-related indicators. One hundred eighty days after macaques received BMMSC treatment, haemoxylin and eosin (HE) staining was performed to observe the morphology and structure of aortic arches. Results: Compared to infant and young control macaques, aged macaques showed erythema on the face, dry skin, reduced amounts of hair on the head and back, and paleness. Cultured BMMSCs from the 4th passage (P4 BMMSCs) were grown in accordance with standards used to culture mesenchymal stem cells. After BMMSC treatment, the assessed aortic arches showed no calcium salt deposition or cell necrosis, and the characteristics of the serum protein expression profile tended to be similar to that of the infant and young groups, with the expression of 41 proteins upregulated with age and that of 30 proteins downregulated with age but upregulated after BMMSC treatment. Moreover, we identified 44 significantly differentially expressed proteins between the aged model and treatment groups; 11 of the upregulated proteins were related to vascular ageing, neuronal ageing and haematopoiesis, and 33 of the downregulated proteins were associated with neuronal ageing, cardiovascular disease, and tumours. Interestingly, S100 expression in serum was significantly decreased, COMP expression was significantly increased, NKAP expression reappeared, and LCN2, CSF1R, CORO1C, CSTB and RSU-1 expression disappeared after BMMSC treatment. Conclusion: BMMSCs can reverse ageing-related serum protein expression.

Background: Heatstroke (HS) is a serious disease caused by central nervous system (CNS) injuries, such as delirium, convulsion, and coma. Currently, mesenchymal stem cells (MSCs) have demonstrated novel neuroprotective effects; therefore, this research explores the neuroprotective effects and mechanisms of MSCs against HS injury. Methods: HS rat models were induced in a 40°C and 65% humidity environment until the rectal temperature reached 42°C. The verified HS injury model rats were divided into the HS and MSCs-treated groups. Each rat in the treated group was infused with 1x10⁶ MSCs suspended in 0.3 ml physiological saline via the tail vein. The HS- or MSCs-treated rats were further divided into early-stage (3d) and late-stage (28d). HS rat models were induced by a high-temperature and high-humidity environment at a specific time, the mortality was analyzed, and an automatic biochemical analyzer measured levels of liver and kidney function indicators in the blood. The neurons' morphologic changes were observed through Nissl staining, and neurological deficit scores were performed. Moreover, the levels of inflammatory factors in brain tissue were measured using a multi-cytokine detection platform, and the expression of BDNF, phosphorylated TrkB and P38 were detected by the Western Bolt. Results: MSCs injection significantly reduced mortality and alleviated liver and kidney function. Moreover, the neurological deficit and neuronic edema of the hippocampus caused by HS at 3d and 28d were significantly ameliorated by MSCs administration. Specifically, the injection of MSCs inhibited high levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and IL-17A caused by HS but elevated the levels of IL-10 and IL-13 in the early period (3d); while in the later period (28d), MSCs significantly increased the levels of IL-10 and IL-13 continuously and inhibited the high level of IL-17A. Furthermore, MSCs injection increased the expressions of BDNF and phosphorylated TrkB (BDNF receptor), meanwhile inhibiting the expression of phosphorylated P38 (inflammatory factor) in the brains of HS rats in the early period (3d) but had no significant influence on the later period (28d). Conclusion: These results suggested that MSCs injection may provide therapeutic effects for HS in rats by improving liver and kidney function and reducing CNS damage. Moreover, MSCs injection inhibited the brain inflammatory response of HS rats, and the BDNF-TrkB and P38/MAPK signal pathways may be involved, providing a potential mechanism for HS therapy by MSCs administration.

Objective: The purpose of our study was to compare the quality of life (QOL) of patients with hematopoietic stem cell transplantation (HSCT) for more than 2 years for β -thalassemia major (β-TM) with that of β-TM patients with conventional therapy (blood infusion and iron chelation) and that of the general population. Methods: This was a cross-sectional comparative study on the QOL of 225 β-TM patients treated with blood transfusion and iron chelation therapy, 133 β-TM patients who had undergone HSCT or 270 ageand sex-matched healthy individuals from Guangxi, China. Child-self and parent-proxy reports of the PedsQL 4.0 Generic Core Scales were used to prospectively evaluate QOL. Results: The incidence of acute GVHD was 14.3% (grade III-IV in 4.5% of patients), and that of chronic GVHD was 3.8%. This was lower than that of previous studies since the inclusion of anti-thymocyte globulin (ATG). Patients who underwent transplantation from a voluntary donor had higher QOL scores and lower rates of acute GVHD, chronic GVHD and comorbidities than those receiving stem cell sources from an HLA mismatched related donor (haploidentical donor). Transplants with PBSCs or UCBT, PBSCT+BMT, BMT, or BMT+UCBT as stem cell sources did not have any impact on QOL. The QOL of β-TM patients was very similar to that of the general population. More complications (P<0.001), shorter post-transplantation time (P<0.001), and older age at HSCT (P=0.01) were associated with poorer child QOL (P=0.020). Additional analyses investigating QOL of β-TM patients receiving conventional treatment with β-TM revealed poorer outcomes than the cohort of transplanted patients. Conclusion: β-TM patients can be cured by HSCT and regain QOL as good as that of the general population. β-TM patients are suggested to undergo HSCT as soon as possible to avoid complications related to iron overload and blood infusion.

Background: Proteomic is capable of elucidating complex biological systems through protein expression, function, and interaction under a particular condition. Objective: This study aimed to determine the potential of ascorbic acid alone in inducing differentially expressed osteoblast-related proteins in dental stem cells via the liquid chromatography-mass spectrometry/ mass spectrometry (LC-MS/MS) approach. Methods: The cells were isolated from deciduous (SHED) and permanent teeth (DPSC) and induced with 10 μg/mL of ascorbic acid. Bone mineralisation and osteoblast gene expression were determined using von Kossa staining and reverse transcriptase-polymerase chain reaction. The label-free protein samples were harvested on days 7 and 21, followed by protein identification and quantification using LC-MS/MS. Based on the similar protein expressed throughout treatment and controls for SHED and DPSC, overall biological processes followed by osteoblast-related protein abundance were determined using the PANTHER database. STRING database was performed to determine differentially expressed proteins as candidates for SHED and DPSC during osteoblast development. Results: Both cells indicated brownish mineral stain and expression of osteoblast-related genes on day 21. Overall, a total of 700 proteins were similar among all treatments on days 7 and 21, with 482 proteins appearing in the PANTHER database. Osteoblast-related protein abundance indicated 31 and 14 proteins related to SHED and DPSC, respectively. Further analysis by the STRING database identified only 22 and 11 proteins from the respective group. Differential expressed analysis of similar proteins from these two groups revealed ACTN4 and ACTN1 as proteins involved in both SHED and DPSC. In addition, three (PSMD11/RPN11, PLS3, and CLIC1) and one (SYNCRIP) protein were differentially expressed specifically for SHED and DPSC, respectively. Conclusion: Proteome differential expression showed that ascorbic acid alone could induce osteoblastrelated proteins in SHED and DPSC and generate specific differentially expressed protein markers.

Objectives: The aim of this systematic review and meta-analysis is to analyze clinical trials on the use of autologous stem cell [SC] injection for the treatment of stress urinary incontinence [SUI] in humans. Methods: We analyzed the effect in terms of UI improvement and continence recovery after treatment. A literature search was performed following the PRISMA guidelines. Entry into the analysis was restricted to data collected from clinical prospective trials on humans, including female and male patients with SUI. We performed a cumulative meta-analysis to explore the trend in the effect size across different groups at follow-up. Available data were compared in terms of Event Rate [ER] for the percentage of pad-free patients. Results: 12 trials were enclosed in the analysis. The sample size of patients with SUI ranged from 5 to 123 cases, mainly female cases. Autologous muscle-derived stem cells [MDSCs] were used in 9 and adipocyte- derived SCs [ADSC] in 3 trials. Considering a random effect model, ER of continence recovery was 0.41 [95%CI 0.29 - 0.54], with similar results between the ADSC [ER, 0.40;95%CI 0.12 – 0.69] and the MDSC group [ER 0.41; 95%CI 0.27-0.55] [I2 84.69%; Q 104.69 - p<0.01] [Test of group differences p=0.96]. Conclusion: Autologous MDSC or ADSC injection to treat SUI is demonstrated to be a safe procedure and a 41% mean rate of continence recovery is described. A higher effort should be produced to design better clinical trials, objectively evaluating either modifications inside the urethral sphincter or long-term functional results in terms of pad test and UI questionnaires.