A Brief Overview of Global Trends in MSC-Based Cell Therapy

Stem Cell Reviews and Reports, Год журнала: 2022, Номер 18(5), С. 1525 - 1545

Опубликована: Март 28, 2022

Язык: Английский

---

Culture-expanded mesenchymal stromal cell therapy: does it work in knee osteoarthritis? A pathway to clinical success

Cellular and Molecular Immunology, Год журнала: 2023, Номер 20(6), С. 626 - 650

Опубликована: Апрель 25, 2023

Abstract Osteoarthritis (OA) is a degenerative multifactorial disease with concomitant structural, inflammatory, and metabolic changes that fluctuate in temporal patient-specific manner. This complexity has contributed to refractory responses various treatments. MSCs have shown promise as multimodal therapeutics mitigating OA symptoms progression. Here, we evaluated 15 randomized controlled clinical trials (RCTs) 11 nonrandomized RCTs using culture-expanded the treatment of knee OA, found net positive effects on pain (improving function 12/15 relative baseline 11/15 control groups at study endpoints) cartilage protection and/or repair (18/21 studies). We examined MSC dose, tissue origin, autologous vs. allogeneic origins well patient phenotype, endotype, age, sex level severity key parameters parsing effectiveness. The relatively small sample size 610 patients limited drawing definitive conclusions. Nonetheless, noted trends toward moderate higher doses select phenotypes leading structural improvements or preservation. Evidence from preclinical studies supportive anti-inflammatory immunomodulatory effects, but additional investigations immunomodulatory, chondroprotective other mechanisms action are needed. hypothesize basal “fitness” correlates efficacy, this hypothesis needs be validated future studies. conclude roadmap articulating need match an subset defined by molecular endotype phenotype basally “fit” engineered-to-be-fit-for-OA well-designed, data-intensive advance field.

Язык: Английский

---

Harnessing knee joint resident mesenchymal stem cells in cartilage tissue engineering

Acta Biomaterialia, Год журнала: 2023, Номер 168, С. 372 - 387

Опубликована: Июль 21, 2023

Osteoarthritis (OA) is a widespread clinical disease characterized by cartilage degeneration in middle-aged and elderly people. Currently, there no effective treatment for OA apart from total joint replacement advanced stages. Mesenchymal stem cells (MSCs) are type of adult cell with diverse differentiation capabilities immunomodulatory potentials. MSCs known to effectively regulate the microenvironment, promote regeneration, alleviate symptoms. As result, they promising sources therapy. Recent studies have revealed presence resident synovial fluid, membrane, articular cartilage, which can be collected as knee joint-derived (KJD-MSC). Several preclinical demonstrated that KJD-MSCs great potential treatment, whether applied alone, combination biomaterials, or exocrine MSCs. In this article, we will review characteristics joints, including their cytological characteristics, such proliferation, differentiation, abilities, well biological function MSC exosomes. We also discuss use tissue engineering introduce concept new generation cell-based therapy, engineering, gene editing techniques create KJD-MSC derivative exosomes improved functionality targeted delivery. These advances aim maximize efficiency provide strategies overcome bottleneck This research insights into medicinal benefit Joint Stem Cells (MSCs), specifically on its ability. Through review, community further realize promoting mesenchymal cells, especially progenitor/MSC-like progenitor (CPSC), preventive measure against osteoarthritis injury. People medical institutions may consider derived an alternative approach degeneration. Moreover, discussion presented study convey valuable information future explore benefits MSC.

Язык: Английский

---

The MSC-EV-microRNAome: A Perspective on Therapeutic Mechanisms of Action in Sepsis and ARDS

Cells, Год журнала: 2024, Номер 13(2), С. 122 - 122

Опубликована: Янв. 9, 2024

Mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (EVs) have emerged as innovative therapeutic agents for the treatment of sepsis acute respiratory distress syndrome (ARDS). Although their potential remains undisputed in pre-clinical models, this has yet to be translated clinic. In review, we focused on role microRNAs contained EVs, EV microRNAome, contribution mechanisms action. The evidence that miRNA transfer EVs a overall effects is compelling. However, several questions remain regarding how reconcile stochiometric issue low copy numbers miRNAs present particles, different delivered simultaneously interact with targets within recipient cells, best or combination use therapy, potency markers, biomarkers efficacy Here, offer molecular genetics systems biology perspective function microRNAs, action, potential.

Язык: Английский

---

Translational potential of mesenchymal stem cells in regenerative therapies for human diseases: challenges and opportunities

Stem Cell Research & Therapy, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 26, 2024

Advances in stem cell technology offer new possibilities for patients with untreated diseases and disorders. Stem cell-based therapy, which includes multipotent mesenchymal cells (MSCs), has recently become important regenerative therapies. MSCs are progenitor that possess the ability to undergo vitro self-renewal differentiate into various lineages. have demonstrated promise several areas, such as tissue regeneration, immunological modulation, anti-inflammatory qualities, wound healing. Additionally, development of specific guidelines quality control methods ultimately result therapeutic application been made easier by recent advancements study MSC biology. This review discusses latest clinical uses obtained from umbilical cord (UC), bone marrow (BM), or adipose (AT) treating human pulmonary dysfunctions, neurological disorders, endocrine/metabolic diseases, skin burns, cardiovascular conditions, reproductive this offers comprehensive information regarding targeted therapies utilizing MSCs. It also presents examines concept origin its potential impact on function downstream applications. The ultimate aim research is facilitate translational applications

Язык: Английский

---

Clinical-grade extracellular vesicles derived from umbilical cord mesenchymal stromal cells: preclinical development and first-in-human intra-articular validation as therapeutics for knee osteoarthritis

Journal of Nanobiotechnology, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 13, 2025

Osteoarthritis (OA) is a joint disease characterized by articular cartilage degradation. Persistent low-grade inflammation defines OA pathogenesis, with crucial involvement of pro-inflammatory M1-like macrophages. While mesenchymal stromal cells (MSC) and their small extracellular vesicles (sEV) hold promise for treatment, achieving consistent clinical-grade sEV products remains significant challenge. This study aims to develop fully characterized, reproducible, batches derived from umbilical cord (UC)-MSC the treatment while assessing its efficacy safety. Initially, standardized, research-grade manufacturing protocol was established ensure production. UC-MSC-sEV characterization under non-cGMP conditions showed miRNA protein profiles, suggesting potential standardized manufacturing. In vitro studies evaluated efficacy, safety, potency sEV; animal confirmed effectiveness vitro, polarized macrophages an anti-inflammatory M2b-like phenotype, through STAT1 modulation, indicating create environment in affected joints. silico sEV's immunosuppressive signature proteome analysis. mouse model, injected intra-articularly (IA) induced hyaline regeneration, validated histological μCT analyses. The unique detection signals within knee over time highlights safety profile confirming retention joint. product development involved refining, standardizing, validating processes compliance GMP standards. initial assessment via IA administration first-in-human no adverse effects after 12 month follow-up period. These results support progress this sEV-based therapy early-phase clinical trial, details which are presented discussed work. provides data on using as local OA, highlighting regenerative properties preclinical proof-of-principle application.

Язык: Английский

---

Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Июнь 9, 2022

MSCs products as well their derived extracellular vesicles, are currently being explored advanced biologics in cell-based therapies with high expectations for clinical use the next few years. In recent years, various strategies designed improving therapeutic potential of mesenchymal stromal cells (MSCs), including pre-conditioning enhanced cytokine production, improved cell homing and strengthening immunomodulatory properties, have been developed but manufacture handling these therapy medicinal (ATMPs) remains insufficiently studied, available data mainly related to non-industrial processes. present article, we will review this topic, analyzing current information on specific regulations, selection living donors from different sources (bone marrow, adipose tissue, umbilical cord, etc.), in-process quality controls ensuring efficiency safety during all stages manual automatic (bioreactors) manufacturing process, cryopreservation, banks, medicines, transport systems ATMPs, among other aspects, according European US legislation. Our aim is provide a guide better, homogeneous cellular special reference MSCs.

Язык: Английский

---

Manufacturing artificial bone allografts: a perspective.

PubMed, Год журнала: 2022, Номер 3(1), С. 65 - 80

Опубликована: Янв. 1, 2022

Bone grafts have traditionally come from four sources: the patients' own tissue (autograft), a living or cadaveric human donor (allograft), animal donors (xenograft) and synthetic artificial biomaterials (ceramics, cement, polymers, metal). However, all of these advantages drawbacks. The most commercially successful bone so far are allografts, which hold 57% current graft market; however, disease transmission scarcity still significant drawbacks limiting their use. Tissue-engineered great potential, in stem cells synthetical combined to produce bone-like vitro, but this is yet be approved for widespread clinical practice. It hypothesised that allografts can mass-manufactured replace conventional through refined engineering prior decellularisation. This review article aims literature on (1) allograft preparation; (2) including use as substitute scaffolds, with osteogenic vitro; (3) potential manufacturing processes, mass production engineered tissue, enhancement, decellularisation, sterilisation safety assurance regulatory approval. From assessments, practical route map proposed.

Язык: Английский

---

Bone Marrow Mesenchymal Stem Cells for Heart Failure Treatment: A Systematic Review and Meta-Analysis

Heart Lung and Circulation, Год журнала: 2023, Номер 32(7), С. 870 - 880

Опубликована: Март 3, 2023

Язык: Английский

---

Progress and emerging techniques for biomaterial-based derivation of mesenchymal stem cells (MSCs) from pluripotent stem cells (PSCs)

Biomaterials Research, Год журнала: 2023, Номер 27(1)

Опубликована: Фев. 9, 2023

Abstract The use of mesenchymal stem cells (MSCs) for clinical purposes has skyrocketed in the past decade. Their multilineage differentiation potentials and immunomodulatory properties have facilitated discovery therapies various illnesses. MSCs can be isolated from infant adult tissue sources, which means they are easily available. However, this raises concerns because heterogeneity among MSC limits their effective use. Variabilities arise donor- tissue-specific differences, such as age, sex, source. Moreover, adult-sourced limited proliferation potentials, hinders long-term therapeutic efficacy. These limitations prompted researchers to develop a new method generating MSCs. Pluripotent (PSCs), embryonic induced PSCs (iPSCs), differentiate into types cells. Herein, thorough review characteristics, functions, importance is presented. existing sources MSCs, including adult- infant-based compared. most recent techniques deriving iPSCs, with focus on biomaterial-assisted methods both two- three-dimensional culture systems, listed elaborated. Finally, several opportunities improved efficiently producing aim advancing applications described.

Язык: Английский

---