The issue of heterogeneity of MSC-based advanced therapy medicinal products–a review

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 26, 2024

Mesenchymal stromal stem cells (MSCs) possess a remarkable potential for numerous clinical applications due to their unique properties including self-renewal, immunomodulation, paracrine actions and multilineage differentiation. However, the translation of MSC-based Advanced Therapy Medicinal Products (ATMPs) into clinic has frequently met with inconsistent outcomes. One suspected reasons this issue is inherent extensive variability that exists among such ATMPs, which makes interpretation efficacy difficult assess, as well compare results various studies. This stems from differences in tissue sources, donor attributes, variances manufacturing protocols, modes administration. MSCs can be isolated tissues bone marrow, umbilical cord, adipose others, each its phenotypic functional characteristics. While different sources do share common features, they also exhibit distinct gene expression profiles properites. Donor-specific factors age, sex, body mass index, underlying health conditions influence MSC phenotype, morphology, differentiation function. Moreover, variations preparation products introduces additional heterogeneity result cell culture media composition, presence or absence added growth factors, use serum supplements culturing techniques. Once are formulated, storage protocols play pivotal role efficacy. Factors affect viability include concentration, delivery solution importantly, post-thawing where applicable. Ensuing, administration critically distribution functionallity administered cells. As therapies continue advance through trials, implication strategies reduce product imperative. Central addressing these challenges need precise prediction responses, require well-defined populations harmonized assessment specific functions. By issues by meaningful approaches, as, e.g., pooling, field overcome barriers towards more consistent effective therapies.

Language: Английский

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Graphene-based materials: an innovative approach for neural regeneration and spinal cord injury repair

RSC Advances, Journal Year: 2025, Volume and Issue: 15(13), P. 9829 - 9853

Published: Jan. 1, 2025

This review explores the pathology of SCI and characteristics GBMs, focusing on recent in vitro vivo research their mechanism, biocompatibility, toxicity, biodegradability.

Language: Английский

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Micro electrical fields induced MSC-sEVs attenuate neuronal cell apoptosis by activating autophagy via lncRNA MALAT1/miR-22-3p/SIRT1/AMPK axis in spinal cord injury

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Nov. 27, 2023

Language: Английский

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Engineering Cells for Cancer Therapy

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(16), P. 2358 - 2371

Published: Aug. 2, 2024

ConspectusCells, particularly living cells, serve as natural carriers of bioactive substances. Their inherent low immunogenicity and multifunctionality have garnered significant attention in the realm disease treatment applications, specifically within domains cancer immunotherapy regenerative tissue repair. Nevertheless, several prominent challenges impede their swift translation into clinical including obstacles related to large-scale production feasibility high utilization costs. To address these issues comprehensively, researchers proposed notion bionic cells that are synthetically generated through chemical or biosynthetic means emulate cellular functions behaviors. However, artificial cell strategies encounter difficulties fully replicating intricate functionalities exhibited by while also grappling with complexities associated design implementation for purposes. The convergence disciplines has facilitated reform a range approaches, chemical-, biological-, genetic-, materials-based methods. These techniques can be employed impart specific enhance efficacy therapy. For example, engineered gene transduction, surface modifications, endocytosis drugs delivery systems, membrane fusion. concept presents promising avenue enhancing control over thereby therapeutic concurrently mitigating toxic side effects ultimately facilitating realization precision medicine.In this Account, we present comprehensive overview our recent research advancements field cells. Our work involves application biological engineering manipulate endogenous therapeutics drug instance, avoid laborious process isolating, modifying, expanding

Language: Английский

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The Current Update of Conventional and Innovative Treatment Strategies for Central Nervous System Injury

Biomedicines, Journal Year: 2024, Volume and Issue: 12(8), P. 1894 - 1894

Published: Aug. 19, 2024

This review explores the complex challenges and advancements in treatment of traumatic brain injury (TBI) spinal cord (SCI). Traumatic injuries to central nervous system (CNS) trigger intricate pathophysiological responses, frequently leading profound enduring disabilities. article delves into dual phases injury-primary impacts subsequent secondary biochemical cascades-that worsen initial damage. Conventional treatments have traditionally prioritized immediate stabilization, surgical interventions, supportive medical care manage both primary damage associated with injuries. We explore current management strategies, emphasizing crucial role rehabilitation promising potential stem cell therapies immune modulation. Advances therapy, gene editing, neuroprosthetics are revolutionizing approaches, providing opportunities not just for recovery but also regeneration impaired neural tissues. aims emphasize emerging therapeutic strategies that hold promise enhancing outcomes improving quality life affected individuals worldwide.

Language: Английский

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An overview of stem cells and cell products involved in trauma injury

Regenerative Therapy, Journal Year: 2025, Volume and Issue: 29, P. 60 - 76

Published: March 11, 2025

Language: Английский

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Advances and New Therapies in Traumatic Spinal Cord Injury

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(7), P. 2203 - 2203

Published: March 24, 2025

Recovery from traumatic spinal cord injury (tSCI) is challenging due to the limited regenerative capacity of central nervous system restore cells, myelin, and neural connections. At clinical level, fundamental pillars treatment are reduction in secondary damage (neuroprotection) rehabilitation; these tools we have mitigate disability caused by (SCI). To date, treatments on which neuroprotection has been based prevention acute respiratory failure avoid hypoxia, early hemodynamic control, neuroprotective drugs surgical management. Optimizing control ensure adequate perfusion may be key management SCI. While agents like methylprednisolone fallen into disuse, several promising therapies currently being tested trials. In terms treatment, although their impact neurological recovery remains debated, appropriate bone decompression followed duroplasty selected cases increasingly recommended. Advances cell hold significant potential for enhancing both functional outcomes SCI patients. Moreover, emerging neuromodulation techniques, such as transcutaneous epidural stimulation, along with innovations rehabilitation technologies-such robotic systems exoskeletons-are becoming indispensable improving locomotion overall mobility individuals This article provides an update advances against tSCI, cellular therapies, new therapies.

Language: Английский

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Guide for Cell Therapy in Human Chronic Spinal Cord Injury

Tissue Engineering Part C Methods, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Based on various research, different cells are effective for improving the symptoms and paraclinical indicators of patients with chronic spinal cord injury (SCI). A big gap in front researchers doctors is to know source, number required injection, delivery method, complementary treatments. We extracted desired data (number cells, autologous or allogeneic source cell extraction, treatments) from 40 clinical trials, which checked recorded 17 scores at least two studies. The most common 11 were bone marrow hematopoietic stem mesenchymal cell. mean effect was more plasma as treatment. Then highest therapy, treatment being methylprednisolone. (106/kg), (autologous), method (intrathecal) similar both types. No life-threatening consequences death recorded. This guideline helps choose appropriate therapy SCI.

Language: Английский

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Cell Therapy for Spinal Cord Injury

Published: Jan. 1, 2025

Language: Английский

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Multiroute administration of Wharton’s jelly mesenchymal stem cells in chronic complete spinal cord injury: A phase I safety and feasibility study

World Journal of Stem Cells, Journal Year: 2025, Volume and Issue: 17(5)

Published: May 23, 2025

BACKGROUND Traumatic spinal cord injury (SCI) is a life-altering condition that results in long-term complications, including progressive neurodegeneration and atrophy. It presents significant unmet medical need with extensive social economic burdens. AIM To evaluate the safety preliminary efficacy of allogeneic mesenchymal stem cells derived from Wharton’s jelly (WJ-MSCs) patients chronic complete SCI. The primary objective was to assess whether WJ-MSCs could facilitate neurological recovery improve quality life this patient population. METHODS This open-label, multicenter phase I study investigated effects administering via three delivery routes: Intrathecal (for localized targeting); intramuscular targeting end organ); intravenous systemic immunomodulation). While all routes were used concurrently enhance therapeutic synergy, neurological, sensory, functional scales overall efficacy. Participants SCI (duration at least 6 months) who had impairment disability eligible for inclusion. administered twice monthly 2 months, each route receiving dose 1 × 106 cells/kg. Patients closely monitored year following treatment. RESULTS At baseline, participants displayed considerable deficits, as indicated by scores: Functional independence measure 77.5 ± 2.26; Modified Ashworth Scale 15.83 4.83; American Spinal Injury Association (ASIA) Motor score 1.67 2.66; ASIA Light Touch Pin-Prick scores 62 18.42 each; Wexner Incontinence Score 20; Qualiveen Short Form, validated questionnaire specifically designed impact urinary dysfunction on individuals SCI, 32. Following WJ-MSC therapy, improvements observed functions over 1-year follow-up. Notably, improved significantly (χ = 23.938, P < 0.001), Form demonstrated substantial enhancement (z -2.214, 0.05). CONCLUSION study, conducted without control group, suggests administration through multiple both safe potentially effective However, cannot be solely attributed concurrent pharmacological rehabilitative interventions not controlled. These findings therapy may offer promising approach enhancing function challenging Further research larger cohorts extended follow-up necessary validate these results.

Language: Английский

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