stem cells

Context: 

Recent advances in induced pluripotent stem cells (iPSCs), CRISPR-Cas9 gene editing, nanotechnologies, and artificial intelligence have revolutionized regenerative medicine (RM) as a transformative field for tackling difficult medical problems. These breakthroughs promise specific treatments, proper restoration of tissue function, and substantial improvements in the quality of life for patients whose ailments cannot yet be cured.This review explores cutting-edge advancements in RM platforms such as stem cell therapy, gene editing, 3D bioprinting, and nanotechnology. The study also aims to shed light on the challenges of clinical translation and policy implications, which are crucial for fostering sustainable and progressive advances in the discipline. 

Evidence Acquisition: 

This manuscript draws on cutting-edge research on the development and application of RM technologies. It synthesizes data on stem cells, gene therapy, tissue engineering, the in vitro organoid industry, artificial intelligence (AI), and nanotechnology that illustrate therapeutic potential. It also aims to identify ethical, regulatory, and practical hurdles for translating RM from research to clinical practice.

Breakthroughs such as those in iPSC-derived organoids, CRISPR-Cas9 gene editing, 3D bioprinting, and nanostructured materials exhibit significant promise in preclinical and clinical settings. Platforms such as organ-on-chip and AI tools further enhance drug discovery and treatment monitoring, while biomaterials and scaffold-based approaches enhance tissue repair and regeneration. Nevertheless, despite these advances, challenges persist regarding scale-up, safety, and ethical considerations.

Innovations in RM represent a paradigm shift from purely symptomatic treatments to restorative therapies. Successful integration of RM into clinical practice will require multidisciplinary collaborative work, imposition of rigorous safety protocols, and enabling regulatory frameworks. Addressing these challenges would enable RM to realize its true potential as a foundation for 21st-century healthcare.

Statement of the Problem: 

Success of pulpotomy of primary teeth depends on biological and cytotoxic effects of pulp capping agents. Mineral trioxide aggregate (MTA), Biodentine, calcium enriched mixture (CEM) cement, and ferric sulfate (FS) are among the commonly used pulp capping agents (PCAs) for pulpotomy, and their successful application has been previously evaluated.

This study aimed to compare the cytotoxicity of PCAs against mesenchymal stem cells isolated from human exfoliated deciduous teeth (SHEDs).

In this in vitro study, SHEDs were exposed to MTA, Biodentine, CEM cement, and FS for 24 and 72 hours. The methyl thiazolyl tetrazolium (MTT) assay was performed for five different concentrations of PCAs after 24 and 72 hours of exposure. Data were analyzed by ANOVA.

Generally, the biocompatibility increased by reduction in concentration. All tested concentrations showed higher biocompatibility at 72 hours compared with 24 hours (p< 0.0001). Comparison of cytotoxicity of different biomaterials revealed no significant difference at any time point (p> 0.05).

In general, the cytotoxicity of MTA, Biodentine, CEM cement, and FS was comparable, with no significant difference. Cytotoxicity decreased over time and by a reduction in concentration of biomaterials. MTA and Biodentine showed maximum biocompatibility followed by FS, and CEM cement.

Mesenchymal stem cell (MSC) transplantation represents a promising approach for treating Alzheimer’s disease (AD). These stem cells, however, have a short lifespan following transplantation into recipient animals. Selenium nanoparticles, due to their size, aid in drug delivery for brain disorders. This study investigated the therapeutic effect of MSCs and polyvinyl alcohol (PVA)-coated selenium nanoparticles (SeNPs) in a rat model of AD.

An Alzheimer-like phenotype was induced through intracerebroventricular (ICV) administration of streptozotocin (STZ).  Rats were assigned to five groups: control, Alz (STZ; 3 mg/kg, 10 μl, ICV), Alz+stem cell (ICV transplantation), Alz+SeNP (0.4 mg/kg, orally), and Alz+stem cell+SeNPs. The ICV administration of STZ mimicked some aspects of AD in the Alz groups. SeNPs were administrated for 30 days following STZ administration. The novel object recognition (NOR) and passive avoidance learning (PAL) tests were used to evaluate cognition and memory. Oxidative stress biomarkers and brain-derived neurotrophic factor (BDNF) were assessed by biochemical analysis, ELISA kits, and Congo red staining, respectively. 

The combined therapy of PVA-coated SeNPs and MSC transplantation was more effective in enhancing memory reacquisition compared to either SeNPs or MSCs alone. The use of stem cells in conjunction with PVA-coated SeNPs significantly boosted anti-oxidant capacity.

The results suggest that the joint treatment with PVA-coated SeNPs and MSCs offers considerable neuroprotection against AD in animal models.

The aim of this study is to review the role of renin-angiotensin in skin regeneration and wound healing with a focus on molecular mechanisms. Angiotensin receptor type 1 (AT1R) are abundant in the wounded area, and thus, lead to the activation of ERK, STAT1, and STAT3 which can lead to epidermal self-renewal. The expression of Renin Angiotensin System (RAS) components was significantly lower in wounds caused by burning, rather than intact skin, noting that RAS is involved in the re-epithelialization of skin. ERK, STAT and STAT3 are the targets of Ang II, indicating that RAS active components are involved in fibroblast, stem cells and keratinocyte migration. The effect of inhibiting the RAS on wound healing is context-dependent. On one hand, it is suggested that inhibiting RAS during this phase may slow down wound healing speed. On the other hand, studies have shown that RAS inhibition in this phase can lead to α-SMA activation, ultimately accelerating the wound healing process. Most of the investigations indicate that the inhibition of RAS with Angiotensin Receptor Blockers (ARBs) and Angiotensin Converting Enzyme (ACE) plays a significant role in tissue remodeling in the last phase of wound healing. It has been shown that the inhibition of RAS can inhibit scar formation and fibrosis through the downregulation of inflammatory and fibrogenic agents, such as TGF-β, SMAD2/3, and TAK1, PDGF-BB, and HSP47. To sum up, that local administration of RAS regulators might lead to less scar formation and inflammation in the last phase of wound closure.

Cryopreservation is a critical enabling technology in stem cell-based therapies, tissue engineering and regenerative medicine that provides stable and long-term storage of organelles, cells, tissues, or any other biological constructs. However, this technology faces challenges, including decreasing cell survival rates and using dimethyl sulfoxide (DMSO), a cytotoxic agent. Moreover, cryopreserving methods are time-consuming and expensive. Various cells and tissues, due to some reasons, such as different metabolic and functional characteristics, respond differentially to the cryopreservation protocols which cause diversities in viability after thawing. This review discusses methods currently used for optimized cryopreservation of hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), adipose-derived stem cells (ASCs), and their advantages and disadvantages. Also, here we discuss about changing the DMSO, freezing rate, pre-freeze storage, and storage temperature that can improve the cryopreservation outcomes. Further studies are still needed to find better cryopreservation methods for stem cells.

There are different types of treatment for eye diseases. Although the majority of eye diseases are curable with primary treatments and surgery, some of degenerative eye damages need regeneration that is not gained by conventional procedures. Stem cells, such as mesenchymal stem cells, human embryonic stem cell?derived retinal pigmented epithelium, and inducible pluripotent stem cells, are now considered one of the most important and safe methods for regeneration of various damaged tissues or organs. However, how will stem cell therapy contribute to regeneration and overcome degenerative eye diseases? This review discusses the regenerative mechanisms, clinical applications, and advantages of different types of stem cells for restoring degenerative eye diseases.

Stem cell therapy is going to become the most widely used type of therapy in regenerative medicine. The stem cell therapy market has grown at an exponential rate in recent years. The purpose of the present paper is to review the stem cell market and the factors affecting it. The methods used included a literature review across reputable databases, and identifying articles and trusted financial reports related to the stem cell therapy market. Results show that the stem cell market growth rate is increasing, so that, the global stem cell market size was valued at US$297 million in 2022 and is anticipated to grow at a compound annual growth rate of 16.8% from 2022 to 2027, driven by factors such as clinical trials with promising results, increasing funding for stem cell research, growing number of technologies and facilities for cell therapy, and rising demand for regenerative medicine. However, the market also faces some challenges such as ethical concerns, regulatory hurdles, and the high cost of stem cell therapies and products. To enhance the development of the market further, policymakers and regulatory bodies must simplify the complicated process of obtaining regulatory approvals for clinical use. However, there are growing concerns about the increasing number of unapproved treatments using stem cells.

One of the causes of infertility is azoospermia. The present study aimed to investigate the effects of swimming exercise, cell therapy, and laser therapy on the expression of genes involved in mitochondrial dynamics in the testicular tissue of azoospermic rats.

In this experimental study, 40 rats (6-8-weeks old) were randomly assigned to 8 groups: 1) Healthy control, 2) patient, 3) sham, 4) laser, 5) exercise, 6) cell, 7) cell + laser, and 8) cell + exercise. The azoospermia model was induced using busulfan at a dose of 40 mg. Stem cells were transplanted once into the vas deferens at a concentration of 1000000 cells per rat. One week after cell transplantation, laser therapy was applied in three repetitions throughout the study period, with an interval of once a week, and after wound healing, the rats swam for 30 minutes a day, 5 days a week, for 8 weeks. To investigate the expression of the studied genes, tissue analysis was performed by the real-time polymerase chain reaction (RT-PCR) technique.

Azoospermia significantly reduced the expression of mitofusin 2 (Mfn2) and significantly increased the expression of dynamin-related protein 1 (Drp1) and muscle-specific RING finger protein 1 (Murf1) in testicular tissue. The use of interventional methods increased the expression of Mfn2, and significantly reduced the expression of Murf1.

Based on the findings, the best changes were observed in the exercise + laser group. Therefore, it can be said that in rats using the azoospermia model, the simultaneous use of regular exercise interventions and laser therapy is the most effective.

The regenerative potential of cardiac stem and progenitor cells is affected by aging and detraining, with the C-Kit cardiac stem cell expressing the Nkx2.5 transcription factor playing a crucial role. Exercise is known to enhance organ regeneration during aging, but the mechanisms involved in new cardiomyocyte formation during physiological cardiac remodeling remain unclear.

Eighteen aged Wistar rats (~440g) were divided into three groups: Control (CO), aerobic training (AT) (5 days per week, 50-75% of maximum speed) for six weeks, and detraining (DT) for four weeks. RT-PCR analysis determined Nkx2.5 gene expression, while immunohistochemical staining identified C-kit-positive and Ki67-positive cardiac progenitor cells.

In heart tissue, C-Kit and Ki67 values significantly differed between the control–training (P=0.001) and training-detraining (P=0.001) groups but not between the control and detraining groups for C-Kit (P=0.502) and Ki67 (P=0.475). Nkx2.5 exhibited a significant difference between control-training (P=0.001), training-detraining (P=0.001), and control-detraining (P=0.006).

Exercise increased the proliferation of heart stem cells, activating C-Kit differentiation and elevating Nkx2.5 expression, thereby delaying the effects of aging. However, detraining significantly impacted heart stem cell function, emphasizing the importance of sustained exercise for optimal cardiac health.