Current Stem Cell Research & Therapy - Volume 20, Issue 3, 2025

While clinical trials exploring stem cells for regenerating periodontal tissues have demonstrated positive results, there is a limited availability of systematic literature reviews on this subject. To gain a more comprehensive understanding of stem cell interventions in periodontal regeneration, this meta-analysis is undertaken to assess the beneficial effects of stem cells in human periodontal regeneration.

“PubMed,” “PubMed Central,” “Web of Science,” “Embase Scopus” “Wanfang,” and “CNKI,” were used to extract clinical studies related to the utilization of stem cells in repairing periodontal tissue defects. This search included studies published up until October 5, 2023. The inclusion criteria required the studies to compare the efficacy of stem cell-based therapy with stem cell-free therapy for regenerating periodontal tissues. Meta-analysis was conducted using Review Manager software (version 5.4).

This meta-analysis synthesized findings from 15 selected studies investigating the impact of stem cell interventions on periodontal tissue regeneration. The “stem cell” group displayed a substantial reduction in clinical attachment level (CAL) compared to the “control” group within 3 to 12 months post-surgery. However, no significant differences in CAL gain were found between groups. Probing pocket depth (PPD) significantly decreased in the “stem cell” group compared to the “control” group, particularly for follow-up periods exceeding 6 months, and dental stem cell treatment exhibited notable improvements. Conversely, no significant differences were observed in PPD reduction. Gingival recession (GR) significantly decreased in the “stem cell” group compared to the “control” group at 3 to 12 months post-surgery. No significant differences were observed in GR reduction between groups. No significant differences were identified in cementoenamel junction-bone distance reduction, infrabony defect reduction, or bone mineral density increase between the two groups. Furthermore, no significant changes were observed in the gingival index, plaque index, or width of keratinized gingiva.

In conclusion, while stem cell-based therapy offers promising prospects for periodontal defect treatment, there are notable limitations in the current body of research. Larger, multicenter, double-blind RCTs with robust methodologies are needed to provide more reliable evidence for stem cell-based intervention in periodontitis.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder with symptoms including tremor and bradykinesia, while traditional dopamine replacement therapy and hypothalamic deep brain stimulation can temporarily relieve patients’ symptoms, they cannot cure the disease. Hence, discovering new methods is crucial to designing more effective therapeutic approaches to address the condition. In our previous study, we found that exosomes (Exos) derived from human umbilical cord mesenchymal stem cells (hucMSCs) repaired a PD model by inducing dopaminergic neuron autophagy and inhibiting microglia. However, it is not clear whether its therapeutic effect is related to inhibiting apoptosis by inhibiting caspase-3 expression.

Three intervention schemes were used concerning previous literature, and the dosage of each scheme is the same, with different dosing intervals and treatment courses and to compare the aspects of behavior, histomorphology, and biochemical indexes. To predict and determine target gene enrichment, high-throughput sequencing and miRNA expression profiling of exosomes, GO and KEGG analysis, and Western blot were used.

Exos labeled with PKH67 were found to reach the substantia nigra through the blood- brain barrier and existed in the liver and spleen. 6-hydroxydopamine (6-OHDA) induced PD rats were treated with Exos every two days for one month, which alleviated the asymmetric rotation induced by morphine, reduced the loss of dopaminergic neurons in the substantia nigra, and increased dopamine levels in the striatum. The effect became more significant as the treatment time was extended to two months. These results suggest that hucMSCs-Exos can inhibit the 6-OHDA-induced neuron damage in PD rats, and its neuroprotective effects may be mediated by inhibiting cell apoptosis. Through high-throughput sequencing of miRNA, potential targets for Exos to inhibit apoptosis may be BAD, IKBKB, TRAF2, BCL2, and CYCS.

The above results indicate that hucMSCs-Exos can inhibit 6-OHDA-induced damage in PD rats, and its neuroprotective effect may be mediated by inhibiting cell apoptosis.

Polycystic ovary syndrome (PCOS) is the most prevalent reproductive endocrine illness in women of reproductive age and is one of the most important causes of female infertility. The pathogenesis of PCOS is complex. Although mesenchymal stem cell therapy is anticipated to be a successful treatment for PCOS, its long-term safety, including tumorigenesis in patients, remains unknown.

This study aimed to confirm the efficacy and safety of human umbilical cord mesenchymal stem cells in improving fertility in PCOS mice.

In this study, dehydroepiandrosterone (DHEA) was used to construct a C56BL/6 mouse PCOS model, human umbilical cord mesenchymal stem cells (hUC-MSCs) were used as a treatment, and the reproductive phenotype was observed in parallel breeding experiments to confirm the efficacy of the treatment. A 4-month follow-up period, final blood tests, and organ histology were carried out to confirm the long-term safety of the treatment.

After hUC-MSCs treatment, the sex hormone disorder of mice was corrected, the morphology and function of the ovary were improved, the number of offspring was significantly increased compared to the control group, and no adverse reactions related to stem cell transplantation such as tumor formation were found within 4 months.

The treatment of hUC-MSCs is safe and effective in treating PCOS over the long term.

In vitro maturation has been considered an approach to mature oocytes derived from women with polycystic ovary syndrome (PCOS). It is suggested that the IVM of oocytes may benefit from mesenchymal stem cells derived conditioned medium (CM-MSC).

The purpose of this study was to determine the efficacy of a cocktail of menstrual blood stem cell (MenSCs)-derived secretome, along with follicular fluid and melatonin, in oocyte maturation and embryo development in PCOS.

Four hundred left germinal vesicle oocytes were collected from 100 PCOS patients and randomly divided into four treatment groups: 1) control, 2) secretome, 3) follicular fluid, and 4) melatonin. Oocyte maturation, fertilization rate, and embryo development were monitored, as well as the expression levels of oocyte-secreted factors (GDF9- BMP15), oocyte maturation (MPK3), and apoptosis (BAX-Bcl2).

The rate of oocyte maturation increased in all test groups, but only the results for the SEC group were significant (P= 0.032). There were no significant differences in oocyte fertilization and embryo yield among groups. However, the quality of embryos significantly increased in the melatonin group compared to the control. Cytoplasmic maturation was confirmed by the expression of oocyte maturation-related genes using Real-time PCR. Additionally, the expression level of BCL-2 was significantly higher in the SEC-FF-MEL group than in the control group (p ≤ 0.01).

Enrichment of IVM media using MenSCs-secretome, particularly along with melatonin, could be an effective strategy to improve oocyte maturation and embryo development in PCOS.

The aim of this study was to investigate the role of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exo) in regulating the intestinal type 2 immune response for either protection or therapy.

hUCMSC-Exo was considered a novel cell-free therapeutic product that shows promise in the treatment of various diseases. Type 2 immunity is a protective immune response classified as T-helper type 2 (Th2) cells and is associated with helminthic infections and allergic diseases. The effect of hUCMSC-Exo on intestinal type 2 immune response is not clear.

C57BL/6 mice were used to establish intestinal type 2 immune response by administering of H. poly and treated with hUCMSC-Exo before or after H. poly infection. Intestinal organoids were isolated and co-cultured with IL-4 and hUCMSC-Exo. Then, we monitored the influence of hUCMSC-Exo on type 2 immune response by checking adult worms, the hyperplasia of tuft and goblet cells.

hUCMSC-Exo significantly delays the colonization of H. poly in subserosal layer of duodenum on day 7 post-infection and promotes the hyperplasia of tuft cells and goblet cells on day 14 post-infection. HUCMSC-Exo enhances the expansion of tuft cells in IL-4 treated intestinal organoids, and promotes lytic cell death.

Our study demonstrates hUCMSC-Exo may benefit the host by increasing the tolerance at an early infection stage and then enhancing the intestinal type 2 immune response to impede the helminth during Th2 priming. Our results show hUCMSC-Exo may be a positive regulator of type 2 immune response, suggesting hUCMSC-Exo has a potential therapeutic effect on allergic diseases.

Clinical application of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is a promising approach for the treatment of heart diseases. However, the tumorigenicity of hiPSC-CMs remains a concern for their clinical applications and the composition of the hiPSC-CM subtypes need to be clearly identified.

In the present study, hiPSC-CMs were induced from hiPSCs via modulation of Wnt signaling followed by glucose deprivation purification. The structure, function, subpopulation composition, and tumorigenic risk of hiPSC-CMs were evaluated by single-cell RNA sequencing (scRNAseq), whole exome sequencing (WES), and integrated molecular biology, cell biology, electrophysiology, and/or animal experiments.

The high purity of hiPSC-CMs, determined by flow cytometry analysis, was generated. ScRNAseq analysis of differentiation day (D) 25 hiPSC-CMs did not identify the transcripts representative of undifferentiated hiPSCs. WES analysis showed a few newly acquired confidently identified mutations and no mutations in tumor susceptibility genes. Further, no tumor formation was observed after transplanting hiPSC-CMs into NOD-SCID mice for 3 months. Moreover, D25 hiPSC-CMs were composed of subtypes of ventricular-like cells (23.19%) and atrial-like cells (66.45%) in different cell cycle stages or mature levels, based on the scRNAseq analysis. Furthermore, a subpopulation of more mature ventricular cells (3.21%) was identified, which displayed significantly up-regulated signaling pathways related to myocardial contraction and action potentials. Additionally, a subpopulation of cardiomyocytes in an early differentiation stage (3.44%) experiencing nutrient stress-induced injury and heading toward apoptosis was observed.

This study confirmed the biological safety of hiPSC-CMs and described the composition and expression profile of cardiac subtypes in hiPSC-CMs which provide standards for quality control and theoretical supports for the translational applications of hiPSC-CMs.

Cartilage has intrinsically limited healing power, and regeneration of cartilage damages has remained a challenge. Secreted products of mesenchymal stem cells have shown a new therapeutic strategies for cartilage injuries. Also it has been observed that low frequency electromagnetic field plays a key role in biological processes.

This research was performed to investigate the synergic effect of mesenchymal stem cell-derived exosomes and low frequency electromagnetic field on chondrogenic differentiation.

In this in vitro study, mesenchymal stem cell-derived exosomes were identified using AFM, SEM, TEM microscopy, and DLS method. Cells were treated in chondrogenic medium by exosomes, low frequency electromagnetic field, and the synergy of both. The cell survival was examined using MTT and Annexin methods, and cartilage differentiation was confirmed by Alcian blue staining. The expression of Sox-9, Acan, Col 2a1 and Col 10a1 genes was examined via Real-Time PCR technique on day 14 post-treatment.

The results confirmed the presence of exosomes with an approximate size of less than 100 nm. The results of Alcian blue revealed greater expression of glycosaminoglycans in the synergic treatment group compared to the other groups. Real-time PCR showed a significant increase in the expression of Sox-9, Acan, and Col 2a1 genes, as well as a significant reduction of Col 10a1 gene expression in the synergic treatment group compared to other groups.

This study indicated that the synergic effect of exosome and low-frequency electromagnetic fields would lead to enhanced chondrogenic differentiation, which can be further explored in future clinical studies.

At present, cyclosporine (CsA) is the first-line treatment for Pure Red Cell Aplasia (PRCA), but CsA administration can be associated with a number of side effects due to its high toxicity. Therefore, it is urgent to explore a safe and effective treatment for elderly patients who cannot be treated with conventional doses of CsA, especially those with multiple complications. Allogeneic Stem Cell Transplantation (ASCT) for PRCA is a promising treatment, but reports of using umbilical cord blood (UCB) are very rare.

In this report, UCB and umbilical cord mesenchymal stem cells (UC-MSCs) combined with low-dose CsA (1-3mg/kg/d) were used to treat 3 elderly patients who were diagnosed with PRCA combined with multiple complications in heart, lung, and renal. The treatments were successful without complications, and 12 months after stem cell infusion, the blood tests of the patients came normal. Moreover, the function of the liver, heart, and kidney continued to be stable.

This report provides an effective regimen of using UCB and UC-MSCs combined with low-dose CsA (1-3 mg/kg/d) to treat PRCA, especially for elderly patients with multiple complications who cannot use the conventional dosage.