Stem cell–based therapies in pediatric disorders: translational advances, unresolved challenges, and future horizons

Harnessing stem cells for regenerative medicine: Current applications and future prospects

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.

Modeling myeloid cell development in health and disease using induced pluripotent stem cells

Key applications of iPSC technology in hemato-oncology are summarized, its major advantages and current limitations are discussed, and emerging directions are highlighted, including scalable iPSC-derived blood cell therapies for inherited and acquired bone marrow failure syndromes and leukemia.

[Advances in the application of stem cells for the treatment of respiratory diseases].

Stem cell-derived exosomes in the therapy of renal diseases: a comprehensive review

Chronic kidney disease (CKD) represents a growing global public health challenge. Current treatments, including pharmacological therapy, immunosuppression, and renal replacement therapy, mainly aim to slow disease progression rather than restore damaged renal tissue, and their efficacy remains limited in many patients. Although stem cell-based therapies have shown regenerative potential, their clinical application is constrained by poor cell survival, limited engraftment, immunogenicity, and potential safety concerns. Stem cell-derived exosomes (SC-exosomes) have therefore attracted increasing attention as a potential cell-free therapeutic strategy. These nanoscale extracellular vesicles can transfer bioactive cargoes, including proteins, lipids, messenger RNAs (mRNAs), and microRNAs (miRNAs), to recipient cells and thereby mediate intercellular communication. Compared with parental stem cell transplantation, SC-exosomes may offer several advantages, including lower immunogenicity, reduced tumorigenic risk, relative stability, and the potential to cross certain biological barriers. This comprehensive review summarizes current research on SC-exosomes in renal diseases, with emphasis on their biological characteristics, therapeutic mechanisms, preclinical evidence, and translational challenges. SC-exosomes may contribute to renal repair by promoting cell survival and regeneration, suppressing inflammation, apoptosis, oxidative stress, and fibrosis, and modulating immune and microvascular responses. We also discuss their potential relevance in multiple renal conditions, including acute kidney injury (AKI), CKD, diabetic nephropathy (DN), and other kidney diseases, as well as the use of exosomal cargoes as candidate diagnostic or prognostic biomarkers. Finally, we outline emerging opportunities and unresolved challenges in this field, including engineered exosomes, targeted delivery, exosome heterogeneity, dose optimization, large-scale production, purification, quality control, and long-term safety. Further standardized preclinical studies and well-designed clinical trials are needed before SC-exosome-based approaches can be translated into routine clinical application.

Guiding pluripotent stem cell therapies past the immune system

Abstract Pluripotent stem cell (PSC)-based therapies hold the potential to unlock cures for numerous diseases, including, but not limited to, Parkinson’s disease, macular degeneration, heart failure, type 1 diabetes, and cancer. Yet as protocols to differentiate PSCs into therapeutically useful cell types have progressed rapidly, immunological rejection remains a major barrier that may limit the widespread use of such PSC-based therapies. In recent years, strategies to genetically modify PSCs to prevent immunological rejection of the downstream cell product have become a point of emphasis. Here, we provide an immunological perspective on these strategies, discussing the breadth of rejection mechanisms that have been uncovered through decades of research and the relative simplicity of designing PSC immune evasion strategies to circumvent these mechanisms. We focus in particular on how these strategies apply to the treatment of type 1 diabetes.

Bioengineered cell therapies for pediatric solid tumors: unmet needs and a measurement-integrated approach.

Pediatric solid tumors continue to pose a major therapeutic challenge, with survival gains lagging behind those achieved in pediatric hematologic malignancies. While traditional approaches have focused on dose escalation and intensification of systemic therapies to improve survival, this strategy is often limited by significant short- and long-term morbidity from intensive multimodal treatment. Because children have developing organs and decades of life ahead, therapeutic strategies must balance durable tumor control with preservation of neurodevelopment, organ function, and quality of life. Immunotherapy has generated significant interest as an alternative to dose escalation; however, clinical translation in pediatric solid tumors has been limited by antigen heterogeneity, tumor plasticity, immune-cold or immune-excluded phenotypes, and a profoundly immunosuppressive tumor microenvironment. Bioengineered cellular therapies, particularly chimeric antigen receptor (CAR) T cells and CAR-modified natural killer (CAR NK) cells, provide a modular platform to address these barriers through synthetic receptor design, multi-antigen targeting, controlled activation, and improved trafficking to anatomically restricted sites such as the brain. However, engineering advances alone are unlikely to achieve durable benefit without parallel integration of quantitative in vivo monitoring capable of reporting biodistribution, persistence, and functional engagement. Non-invasive imaging and measurement-enabled approaches can provide mechanistic insight into therapeutic performance, discriminate between delivery failure and functional dysfunction, and support rational iteration of construct design, dosing, and route of administration. In this perspective, we review the current status of CAR T and CAR NK therapies in pediatric solid malignancies, outline key biological and engineering challenges, and propose a pediatric-centered development framework that integrates controllable cell engineering with quantitative, non-invasive assessment of in vivo behavior. By embedding measurement into the therapeutic design loop and prioritizing long-term safety and developmental outcomes alongside efficacy, next-generation engineered cell therapies may evolve toward adaptable, precision-guided systems capable of improving both survival and quality of life for children.