Current Stem Cell Research & Therapy - Online First

Stem cell therapies are advancing rapidly, requiring robust regulations to ensure safety and ethics. The UAE, with authorities like MOHAP, DOH, DHA, and DHCR, is actively involved in clinical research but faces regulatory inconsistencies across emirates. In contrast, the U.S. (FDA, NIH) and India (CDSCO, ICMR) have unified national frameworks with specific stem cell guidelines. This study compares the UAE’s system with those of the U.S. and India to identify strengths and gaps.

A comparative literature review was conducted using regulatory documents, clinical trial registries, peer-reviewed studies, and interviews. The focus was on analyzing the regulatory frameworks in the UAE, the U.S., and India, especially regarding stem cell clinical research.

The UAE has established ethical review boards and oversight mechanisms but lacks unified national guidelines and consistent application across emirates. In comparison, the U.S. and India have more cohesive, transparent, and accessible regulatory systems for stem cell research.

The UAE’s efforts in promoting stem cell research are notable, but fragmentation among regulatory authorities hampers coordination. Adopting centralized policies, like in the U.S. and India, could improve efficiency, transparency, and compliance. A national registry and stem cell-specific guidelines are also needed.

The UAE has made commendable progress in regulating stem cell clinical research. However, the absence of unified national guidelines and inter-emirate coordination remains a challenge. Learning from the centralized frameworks of the U.S. and India can help bridge these gaps. Strengthening oversight will enhance patient safety, ethical compliance, and global collaboration.

Cell therapy is regarded as a significant and therapeutic strategy for treating spinal cord injury (SCI). This systematic review was conducted to assess Schwann cell (SC) therapy and its effect on functional recovery, axonal regeneration, and remyelination.

By a systematic review study, all associated articles that investigated the effect of Schwann cell therapy on functional recovery, axonal regeneration and remyelination and were published between 1995 and 2024 were evaluated through searching in PubMed, Google Scholar, Scopus and Web of Science. The following keywords were searched: spinal cord injury, Schwann cell therapy, transplantation, functional recovery, axonal regeneration, and remyelination and Boolean operators were used to increase the search results: “(Remyelination OR Regeneration OR Transplantation) AND (Spinal Cord Injury)”, “Spinal Cord Injury AND Schwann cell”, “Spinal Cord Injury AND Schwann cell AND transplantation” and the search was filtered for species, injury type, experimental study, interventional study, clinical trial study, systematic review and meta-analysis study and was limited to articles in English and Persian languages.

The results of studies on animal samples showed significant functional recovery of cases treated using SCs. However, the success of cell therapy in human experiments has not been established; moreover, researchers should consider other therapeutic approaches in addition to cell transplantation, especially combination therapy.

Studies have shown that Schwann cell transplantation into a contused spinal cord can result in axonal regeneration and functional recovery, similar to the repair models involving spinal cord transection. Therefore, an understanding of the results of Schwann cell therapy on functional recovery, axonal regeneration, and remyelination in spinal cord injury is necessary and helpful.

Schwann cell transplantation promotes functional recovery and axonal regeneration in SCI animal models, but human translation requires further investigation, highlighting the need for combinatorial therapies.

Fibroblast growth factor 2 (FGF2) plays a crucial role in regulating the osteogenic differentiation of progenitor cells. However, the process by which this occurs is not yet fully understood. In this study, we aimed to investigate whether FGF2 stimulates the osteogenesis of precursor cells through the yes-associated protein (YAP) and large tumor suppressor kinases 1/2 (LATS1/2).

Human bone marrow stromal cells (hBMSCs) were cultured in osteogenic medium supplemented with FGF2 at concentrations of 2 ng/mL, 10 ng/mL, and 50 ng/mL for 2, 7, or 21 days. Alizarin red staining was performed to identify mineralization after 21 days of culture. RT-qPCR was conducted to detect the mRNA expression of Yap, Lats1, Lats2, Runx2, Bglap, and β-Actin. Immunofluorescence staining was carried out to detect the protein expression of YAP and LATS1/2. Data was analyzed with a p-value set at 0.05.

Mineralization was most significant at 10 ng/ml of FGF2 for 7 days and increased with concentrations of FGF2 from 0 ng/ml to 10 ng/ml for 7 days (p < 0.05) but decreased at the high concentration of 50 ng/ml for 2 days (p < 0.05). mRNA expression of Yap, Runx2, and Bglap increased in concordance with the increasing mineralization levels, but Lats1/2 mRNA decreased. mRNA expression levels were dose-dependent when FGF2 was added for 7 days (p < 0.05) and time-dependent when FGF2 concentration was at 10 ng/ml (p < 0.05). At the protein level, YAP increased while LATS1/2 decreased, indicating that LATS1/2 decreased, and YAP increased at higher mineralization levels when hBMSCs were cultured with 10 ng/ml of FGF2 for 7 days.

Consistent with our results, prior research has also indicated that lower concentrations of FGF2 enhance cell proliferation, thereby increasing the cell population for later osteogenic differentiation. However, excessive expansion can negatively affect differentiation. The mechanism of FGF2 regulation in stem cell osteogenic differentiation needs more exploration.

Optimal concentrations and durations of FGF2 are critical for the osteogenic differentiation of hBMSCs. Moreover, it has been observed that mineralization correlates well with increasing YAP and decreasing LATS1/2 during osteogenic differentiation.

Rheumatoid arthritis (RA) is an inflammatory disease that causes significant disability and persistent inflammation. Currently, there are no appropriate treatments for RA other than systemic immunosuppressants, which have a variety of undesirable effects after long-term use. Thus, this study aims to determine the anti-arthritis effect of chrysin (5,7-dihydroxyflavone) and/or bone marrow-derived mesenchymal stem cells (BM-MSCs), separately and combined, on CFA (complete Freund’s adjuvant)-induced arthritis in rats as an animal model of RA.

Male Wistar rats were subcutaneously injected with 100 μL of CFA/rat/day in the paw of the right hind limb for two consecutive days to induce RA. Arthritic rats received chrysin in an oral dose of 100 mg/kg bw each day, BM-MSCs at 1 × 10⁶ cells/rat once per week in DMEM (Dulbecco’s modified Eagle’s medium) into the lateral tail vein, and a combination for 21 days.

The oral administration of chrysin and intravenous injection of BM-MSCs significantly reduced the increased anteroposterior thickness, volume, and circumference of the right hind paw, as well as serum levels of RF, IL-1β, TNF-α, and IL-17, as well as serum MDA level, besides augmenting serum levels of GPx, GST, GSH, and SOD. The arthritic rats treated with chrysin and/or BM-MSCs exhibited a significant improvement in the elevated expression levels of IκBα, NF-κB p50, and NF-κB p65 proteins in ankle joint articular tissue. Similarly, the histopathological score and histological sections provided additional evidence of the improvement in arthritic lesions.

The treatment with chrysin and BM-MSCs has potential anti-arthritic effects, which may be attributed to their abilities to suppress the inflammation and oxidative stress and enhance the antioxidant defense system. The combinatory effect of chrysin and BM-MSCs was found to be the most effective. However, further clinical studies are required to assess their safety and efficacy in patients with arthritis.

Due to their strong antioxidant and anti-inflammatory properties, the combined administration of chrysin and BM-MSCs was found to be more effective in treating arthritis than either treatment alone in Wistar rats.

Stem cells have recently gained prominence in regenerative medicine, particularly in the treatment of neurological disorders. As a result, Human-induced Pluripotent Stem Cells (hiPSCs) have become a significant focus.

This study aimed to differentiate hiPSCs into neural lineages under in vitro conditions using forskolin and retinoic acid in an induction medium combined with chondroitin 4-sulfate and chondroitinase.

Optimal component concentrations were determined using the MTT assay and acridine orange/ethidium bromide (AO/EB) staining. Subsequently, neural-specific genes (NSE, MAP-2, β-tubulin III, Oligo-2, and GFAP) and proteins (gamma enolase, MAP-2, and β-tubulin III) were assessed using Real-time PCR analysis and immunofluorescence staining to provide a comprehensive evaluation of differentiated cells.

Our study demonstrated a significant enhancement in neural-specific gene and protein markers during the 7th and 14th days of differentiation in the presence of combined chondroitin 4-sulfate and chondroitinase, demonstrating a higher efficacy compared with the application of isolated enzymes or substrates.

These findings emphasize the potential importance of chondroitin 4-sulfate and chondroitinase as important factors in promoting the neural differentiation of hiPSCs. It seems that chondroitin 4-sulfate may activate cellular signaling pathways that are effective in inducing neural differentiation. Our findings in this research provide new opportunities to advance regenerative therapies for neurological disorders.

Parkinson's disease (PD) is a chronic progressive neurodegenerative disease with debilitating clinical presentations. Common therapeutic approaches for symptomatic improvement are often effective for a temporary period of time, after which patients often experience progressive disabilities. Cell replacement therapy is a potential therapeutic method that aims to replace depleted mesencephalic dopaminergic (DA) neurons, which may control symptoms and halt disease progression. Preclinical studies have investigated the efficacy of these PSC-derived DA cells in animal models of PD.

In this study, we comprehensively examine preclinical data on the therapeutic effect of primate PSC-derived DA progenitors on motor deficits in animal models of PD as a precursor for conducting human clinical trials. Relevant articles published before August 14^th, 2023, were obtained from PubMed, Scopus, and Web of Science.

Through several rounds of screening, 46 studies that met our inclusion criteria were included in this study. The quality of each study was assessed using CAMARADES and SYRCLE approaches. Although no included studies were judged to have an overall high risk of bias, several studies exhibited domain-specific methodological limitations. The analyzed studies demonstrate that cell therapy significantly improves motor dysfunction in rodent and non-human primate models of PD.

This systematic review and meta-analysis demonstrate that PSC-based cell therapy significantly improves motor dysfunction in rodent and NHP models of PD and could be a promising approach for halting disease progression, improving behavioral manifestations of the disease, and increasing the overall quality of life in PD.