Aug 2026· Journal of Clinical and Translational Research· pp. 026080013· 0 citations
TL;DR
A comprehensive literature review of preclinical models and clinical trials focusing on mesenchymal, hematopoietic, and pluripotent stem cells, evaluating their efficacy, safety, and manufacturing challenges found stem cell therapies demonstrate remarkable healing potential.
Abstract
Background: Degenerative diseases place an immense burden on global healthcare. Stem cell-based regenerative medicine offers transformative, potentially curative therapies to restore damaged tissues and recover normal physiological function. Aim: This review aims to comprehensively evaluate the therapeutic applications, biological mechanisms, and clinical prospects of stem cells in treating diverse human organ disorders. Methods: We conducted a comprehensive literature review of preclinical models and clinical trials focusing on mesenchymal (MSCs), hematopoietic (HSCs), and pluripotent stem cells (PSCs), evaluating their efficacy, safety, and manufacturing challenges. Results: Cell therapies demonstrate remarkable healing potential. MSCs exhibit potent immunomodulatory effects in inflammatory conditions. HSC transplantation remains the gold standard for hematological disorders and is expanding into targeted gene therapies. PSC-derived cells show promising clinical efficacy in spinal cord injuries, macular degeneration, type 1 diabetes, and heart failure. However, significant hurdles remain, including immune rejection, tumorigenicity, and batch-to-batch variability. Conclusion: Cell therapies represent a paradigm shift from lifelong symptom management to definitive cures. Resolving biological, technical, and regulatory hurdles is imperative for the safe, standardized, and widespread clinical translation of these interventions. Relevance for Patients: For patients suffering from chronic, degenerative, or currently incurable conditions, stem cell therapies represent a transformative clinical paradigm. By facilitating functional tissue regeneration and targeted immunomodulation, these therapies reduce the burden of chronic pharmacotherapy and invasive procedures.
Mesenchymal stem cells (MSCs) reside in various organs and play vital roles in maintaining tissue homeostasis and facilitating regeneration. These cells can be harvested from discarded tissues, expanded in vitro, and utilized as therapeutic agents for immune-related and inflammatory disorders. Their regenerative capabilities are largely mediated through interactions with immune cells. Dental stem cells (DSCs), isolated from multiple dental tissues, exhibit remarkable immunomodulatory properties and have demonstrated therapeutic efficacy in autoimmune and inflammatory diseases. However, the immunosuppressive function of MSCs/DSCs presents a unique challenge in oncology, where it can paradoxically support tumor progression. This review critically analyzes the immunoregulatory pathways involved in inflammatory and immune-related disorders, and directly links these mechanisms to the challenges within the tumor microenvironment. Furthermore, we discuss innovative bioengineering strategies to reprogram MSCs/DSCs or target their pathways for enhanced anticancer efficacy. We highlight the critical clinical limitations and the need for personalized approaches based on distinct DSC subpopulations. A deeper comprehension of this context-dependent functionality is essential for developing safe and effective MSC/DSC-based therapies.
This paper will provide the current information on stem cells used in the treatment of children and the many different types of stem cells, including: hematopoietic stem cells (and their derivatives), mesenchymal stem cells (and their derivatives), induced pluripotent stem cells, embryonic stem cells, tissue-specific progenitor cells, extracellular vesicles, and bioengineered products.
Hany E. Marei· Stem cell research & therape...· 0 citations
Mesenchymal stem cells (MSCs) have attracted considerable attention for clinical translation in regenerative medicine, primarily due to their validated paracrine effects, prominent immunomodulatory properties, and superior multipotent differentiation capabilities. However, the limited homing efficiency and poor post-transplant survival of MSCs severely compromise therapeutic efficacy, thereby giving rise to suboptimal and inconsistent treatment outcomes. To circumvent these critical drawbacks and fully harness the therapeutic potential of MSCs, researchers have incorporated a diverse array of effective strategies, including genetic engineering, preconditioning with cytokines, small molecular compounds or hypoxic stimuli, and scaffold-based culture systems. Given these promising research advances, this review systematically summarizes recent advances in MSC-enhanced therapeutic strategies, and elaborates on their core molecular mechanisms as well as how these mechanisms modulate MSC survival, homing capacity and immunomodulatory efficacy. On this basis, we further analyze the practical applicability of these enhanced MSCs in clinical trials and seek to provide critical insights for the clinical selection of MSC-based enhanced therapies.
Shanshan Zheng, Yukang Huang, Xianli Yang et al.· Frontiers in Cell and Develo...· 0 citations
Highlights What are the main findings? In various clinical trials, largely unmodified mesenchymal stem cell (MSC) therapies have shown limited and inconsistent benefits, highlighting the need for a shift toward MSC products engineered to target specific mechanisms and diseases. Targeted engineering, such as genetic modification, hematopoietic cell E-/L-selectin ligand (HCELL)/CD44 and E-selectin glycoengineering, hypoxic/cytokine preconditioning, biomaterial scaffolding, and MSC-derived extracellular vesicles, may address core limitations of unmodified MSCs by improving homing, persistence, immunomodulation, and resistance to senescence in preclinical models, which may in turn contribute to healthspan-relevant outcomes. What are the implications of the main findings? Disease-matched and combinatorial engineering could establish MSCs as a flexible therapeutic platform for treating age-related diseases and potentially improving healthspan-related outcomes rather than lifespan alone. Clinical translation will depend on standardized manufacturing, validated potency and senescence resistance assays, long-term monitoring of tumorigenicity, and regulatory frameworks suited to aged recipients. Abstract Engineered mesenchymal stem cells (MSCs) have emerged as promising therapeutic platforms for healthspan-relevant applications. As agents of tissue repair and modulators of biological aging, MSCs have been widely studied for their capacity to enhance regeneration, restore immune homeostasis, and reduce chronic inflammation associated with age-related decline. This review examines emerging bioengineering strategies designed to overcome key age-related limitations in MSC homing, survival, and paracrine signaling, which have historically constrained their in vivo efficacy. We discuss major engineering approaches, including genetic modification, surface engineering, metabolic reprogramming, and preconditioning, with particular attention to their contributions to longevity-focused applications. Preclinical studies have demonstrated that engineered MSCs and their extracellular vesicles (EVs) yield measurable improvements in therapeutic performance. Reported benefits include prolonged persistence in inflamed tissues, partial reversal of senescence-associated phenotypes, and modulation of pro-aging inflammatory pathways. While MSC-derived EVs may offer potential safety advantages and could reduce certain risks associated with live-cell administration, this remains to be confirmed in well-controlled clinical studies, and significant challenges persist in terms of manufacturing scalability, cargo consistency, and process standardization. The current literature, which is predominantly preclinical, supports the potential of engineered MSC platforms to improve healthspan-relevant outcomes; direct evidence of healthspan extension in humans is not yet available. However, successful clinical translation will require a standardized manufacturing process to ensure therapeutic safety, reproducibility, and efficacy in age-related conditions.
Anne-Isabelle S. Reme, Mela Lew, Yulexi Y. Ortiz et al.· Cells· 0 citations
Therapeutic approaches employing mesenchymal stem cells (MSCs) have emerged as a promising avenue for investigating treatments for neurological disorders. This strategy aims to capitalize on the biological properties of MSCs to support the repair of damaged neural tissue and modulate pathological processes. This review provides a comprehensive overview of the current clinical evidence regarding MSC applications in major neurological disorders, including Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, spinal cord injury (SCI), and other pertinent disorders. Across clinical studies, MSC administration has generally demonstrated a favorable safety profile and procedural feasibility. However, therapeutic efficacy remains variable and inconsistent across trials. Importantly, differences in MSC sources, manufacturing procedures, delivery routes, dosing strategies, and patient selection contribute substantially to the heterogeneity of reported outcomes. Therefore, the current body of evidence supports the safety of MSC-based interventions, but their clinical effectiveness has not yet been consistently demonstrated. Future progress will depend largely on the standardization of cell preparation and treatment protocols, improved biomarker-driven patient stratification, and rigorously designed large-scale randomized trials.
M. C. Jamali, Alaa Shafie, A. J. Alqahtani et al.· Stem cell research & therape...· 0 citations
Abstract Mesenchymal stem cells (MSCs), as a type of adult stem cells, exhibit robust self-renewal, multi-lineage differentiation, paracrine and immunomodulatory capacities, demonstrating broad application prospects in the treatment of neurodegenerative diseases. This review systematically summarizes the mechanisms of action, therapeutic advances and comparative analyses of various MSCs and their derived extracellular vesicles (EVs) in Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), and discusses the optimization effects of gene modification and pretreatment on therapeutic efficacy. This article not only highlights the advantages of various MSCs and their corresponding EVs, but also provides unique insights into their differentiated therapeutic potential and mechanism of action, which have not been fully elucidated in previous studies. Meanwhile, although current research results are encouraging, this paper also critically points out that existing studies suffer from insufficient elucidation of mechanisms and lack of large-scale clinical trials. Finally, the article prospects future directions of MSC-based therapeutic strategies, including mechanism deepening, treatment optimization and standardization system construction, to promote their translation into clinical application. However, most of the current evidence is still preclinical, and the recognized clinical efficacy in humans is still limited. This is a narrative review. Literature was screened from Web of Science and PubMed by thematic relevance and research quality, without systematic review protocol or meta-analysis.
Lu-Ming Pan, Bao-Cai Liu, Jing-Jian Xu et al.· International Journal of Nan...· 0 citations
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