Alzheimers disease (AD) remains a progressive neurodegenerative disorder with limited disease-modifying treatment approaches. This scoping review aimed to systematically examine and critically evaluate the existing clinical evidence on stem cell therapy for AD, focusing on therapeutic efficacy, safety, cognitive and functional outcomes, neuroimaging, and improvement of biological markers for disease progression. A search of PubMed, Google Scholar, and ClinicalTrials.gov identified 3158 records, of which seven clinical studies met the eligibility criteria. The included studies comprised early-phase clinical trials, pilot studies, and observational studies involving predominantly patients with mild to moderate AD. Mesenchymal, umbilical cord-derived, and telomerase-positive stem cell therapies administered through intravenous, intracerebroventricular, intranasal, and intrathecal routes demonstrated encouraging preliminary signals across cognitive, functional, neuroimaging, and biomarker outcomes. Improvements or stabilization in Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Alzheimer’s disease assessment scale cognitive subscale (ADAS-Cog), and functional measures were reported, alongside reductions in CSF amyloid-β or tau-related biomarkers and evidence of reduced hippocampal atrophy in selected studies. Across the included studies, stem cell therapies showed generally favorable tolerability, with predominantly transient and mild adverse events. Current clinical evidence supports the potential of stem cell therapy as a biologically active and potentially disease-modifying approach for AD. However, definitive conclusions remain limited by small sample sizes, heterogeneous cell products and delivery protocols, methodological variability, and limited long-term follow-up. Future multicenter, Phase IIb/III trials with standardized cell products, administration protocols, outcome measures, and long-term safety monitoring are required to establish clinical efficacy and translational feasibility.
Organ failure remains a leading cause of death, yet organ transplantation cannot meet clinical demand. Although 3D bioprinting enables the fabrication of precise structures, it still lacks programmability and the ability to dynamically regulate. This Review explores how synthetic biology can empower 3D bioprinting to construct functional artificial tissues and organs. Synthetic biology enables cell programming through genetic circuits, intercellular communication systems, and environmental response mechanisms, while programmable biomaterials support dynamic regulation. Combined with functional enhancement strategies in 3D bioprinting, these advancements have effectively improved tissue structure, maturation, and functional integration. The convergence of synthetic biology and 3D bioprinting, by coordinating cell programming, material design, and manufacturing strategies, shifts tissue engineering from static constructs toward adaptive, self-regulating living systems. Although challenges remain, this approach offers new insights for the development of artificial tissues and organs with clinical application value. In addition to therapeutic applications, this integration also holds promise for disease modeling, drug screening, and toxicity assessment.
Radiotherapy serves as a palliative option for alleviating cancer pain but can also elicit chest wall pain following stereotactic body radiotherapy (SBRT). The etiology of chest wall pain remains unclear but may relate to SBRT effects on normal ribs and responses from activated osteoclasts. This review explores potential mechanisms and treatment strategies for this increasingly common complication for patients undergoing radiotherapy. Radiation-induced bone loss is likely multifactorial, involving changes to bone microvasculature, suppressed angiogenesis, osteoblast damage and senescence, as well as increased resorption via activated osteoclasts. Preliminary data suggest that inhibiting osteoclasts may prevent radiation-induced chest wall pain and rib fracture. Our laboratory has identified TGF-βR1 as a potential central mediator of radiation-induced bone loss and pain signaling between osteoclasts and sensory neurons. Advances in radiotherapy have optimized tumor targeting and control. However, radiation-induced musculoskeletal toxicity remains prevalent. Recent findings suggest targeted inhibition of TGF-β signaling between osteoclasts and neurons may offer a therapeutic strategy to mitigate radiation-induced pain.
Mesenchymal stem/stromal cells (MSCs) and probiotics represent two powerful yet independently pursued therapeutic modalities in regenerative medicine. MSCs provide potent immunomodulation and tissue repair through paracrine signaling, while probiotics restore microbial homeostasis and modulate host immunity. This review aims to asses biological and translational rationale for combining these modalities, what preclinical evidence supports their synergy across disease contexts, and what mechanistic, manufacturing, and regulatory barriers currently impede clinical translation. A particular emphasis was placed on neurological indications, the gut-brain-immune axis, and the largely unexplored interface of MSC apoptosis, efferocytosis, and probiotic conditioning. Preclinical evidence demonstrates robust synergy, particularly in inflammatory bowel disease models, where probiotic-primed MSCs exhibit enhanced immunomodulatory capacity through three key mechanisms: (1) metabolite-driven immune licensing favoring regulatory T-cell expansion and efferocytosis modulation (2) bidirectional paracrine and extracellular vesicle-mediated crosstalk, and (3) microenvironment conditioning that optimizes MSC engraftment and function. Promising preclinical data further extend to autoimmune disorders, wound healing, and neurological conditioning, where combined probiotic and MSCs administration demonstrated synergistic neuroprotection in animal models. Metabolic diseases. However, comprehensive review of clinical trial registries reveals a striking translational gap, no registered human trials combining these modalities exist despite extensive preclinical evidence and regulatory approval of MSC monotherapy for perianal Crohn’s disease. The probiotic-MSC alliance represents a scientifically compelling frontier with strong mechanistic rationale and robust preclinical validation, yet remains entirely untested in human clinical trials. The major takeaways are: (1) the gut microbiome functions as a critical upstream modulator of MSC therapeutic efficacy, acting systemically through SCFA licensing, efferocytic amplification, and extracellular vesicle cargo modulation, even where MSCs do not physically reach the intestinal mucosa due to pulmonary first-pass entrapment; (2) the neurological domain, particularly Parkinson’s disease and ischemic stroke, represents a high-priority but empirically unexplored frontier for combination approaches targeting the gut-brain-immune axis; and (3) successful clinical translation will require factorial trial designs in IBD and metabolic disorders, sophisticated GMP-compliant manufacturing infrastructure for combination Live Biotherapeutic Product–Advanced Therapy Medicinal Products, tiered multi-assay potency matrices, and biomarker-driven patient stratification leveraging multi-omics and machine learning. The next five years represent a critical inflection point for translating this powerful biological synergy into meaningful clinical benefit for patients with complex inflammatory and metabolic diseases. The field is advancing toward precision medicine through engineered probiotics, multi-omics patient stratification, and personalized delivery platforms. Machine learning-guided microbiome profiling may enable identification of patient “theratypes” predicting therapeutic response, while novel delivery systems including enteric-coated formulations and programmable ingestible capsules promise optimized spatiotemporal release.
This paper reviews the current understanding of the potential for humans to enter a state of torpor/hibernation, and discusses the possibility of inducing torpor in astronauts for long-duration space travel, including some of the physiological, technological, and ethical considerations associated with its implementation. By exploring means to induce torpor in various human organoid systems, we hope such research can provides insights to comprehensive solutions to overcome some of the major hurdles that limit the potential for human to enter a state of torpor during long-duration deep-space missions, and contribute to the ongoing efforts to make such missions more feasible and safer for astronauts. On future deep space missions such as NASA’s planned missions to the Moon, Mars, and near-Earth asteroids, astronauts will be continuously exposed to environments that are radically different from those on Earth, each presenting multiple logistical and physiological challenges. Beyond the well-documented physiological effects of microgravity, space travelers will encounter a complex radiation environment that may contribute to significant short- and long-term adverse effects on human physiology and increase the risk of cancer and other diseases. Besides these physical challenges, life support systems must also be designed to mitigate psychological impacts of long-term isolation and confinement – all of which collectively pose formidable engineering problems. Hibernation/torpor is a state of prolonged inactivity and metabolic depression used by a wide variety of mammals to survive periods of cold temperatures and food scarcity, including some primates and perhaps even an extinct early line of hominins that lived nearly half a million years ago. Since modern humans share common ancestry with these hominins and hibernating primates, it is likely the human genome encodes the necessary genetic information to hibernate, or at least enter the similar, more transient state of torpor. The reduced body activity, lowered metabolism, and decreased energy requirements that characterize torpor suggest that developing means of inducing such a state in astronauts could address these challenges, including providing a degree of radioprotection. This review explores the potential application of human torpor as a countermeasure to address the many challenges posed by long-duration spaceflight beyond low-Earth orbit (LEO), discusses various natural hibernating model systems for studying means of inducing a torpor-like state in humans, and highlights the vast potential of using human organoids to test and validate mechanisms that govern induction and maintenance of torpor to identify the means to one day safely induce this state in astronauts to provide additional protection from the myriad stressors of spaceflight.
