Unveiling heterogeneity in MSCs: exploring marker-based strategies for defining MSC subpopulations

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 15, 2024

Mesenchymal stem/stromal cells (MSCs) represent a heterogeneous cell population distributed throughout various tissues, demonstrating remarkable adaptability to microenvironmental cues and holding immense promise for disease treatment. However, the inherent diversity within MSCs often leads variability in therapeutic outcomes, posing challenges clinical applications. To address this heterogeneity, purification of MSC subpopulations through marker-based isolation has emerged as promising approach ensure consistent efficacy. In review, we discussed reported markers MSCs, encompassing those developed candidate marker strategies high-throughput approaches, with aim explore viable addressing heterogeneity illuminate prospective research directions field.

Language: Английский

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Novel therapeutic strategies for Asherman's syndrome: Endometrial regeneration using menstrual blood-derived stem cells

Regenerative Therapy, Journal Year: 2025, Volume and Issue: 29, P. 328 - 340

Published: April 7, 2025

Language: Английский

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Mesenchymal stem cell therapy for ischemic cardiomyopathy: Research progress and prospects for application

Deleted Journal, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 13

Published: April 10, 2025

This review aims to explore the research progress and application prospects of mesenchymal stem cells (MSCs) in treatment ischemic cardiomyopathy (ICM). ICM is a severe heart disease characterized by death myocardial due long-term ischemia, leading impaired function. MSCs have become one promising therapeutic methods for treating their unique anti-inflammatory, anti-apoptotic, immunomodulatory, pro-angiogenic properties. Studies shown that can improve function promoting neovascularization, reducing cell apoptosis, inhibiting inflammatory responses, regulating immune reactions. Additionally, be sourced from various tissues, including bone marrow, adipose tissue, umbilical cord/placenta, with different sources possessing distinct characteristics effects. Clinical studies indicated MSC therapy physical capacity left ventricular ejection fraction (LVEF) patients intractable angina, enhance perfusion overall infarction. However, issues such as mechanisms MSCs, optimal source, infusion routes, dose optimization still require further research. Future need address these transform clinical trials routine practice, thereby revolutionizing management prognosis ICM.

Language: Английский

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Orchestration of human multi‐lineage hematopoietic cell development by humanized in vivo bone marrow models

HemaSphere, Journal Year: 2025, Volume and Issue: 9(4)

Published: April 1, 2025

Abstract Hematopoiesis develops in the bone marrow (BM) where multiple interactions regulate differentiation and preservation of hematopoietic stem progenitor cells (HSPCs). Immune‐deficient murine models have enabled analysis molecular cellular regulation human HSPCs, but physiology these is questioned as develop xenogenic microenvironments. In this study, we thoroughly characterized a humanized (h) vivo BM model, developed from fetal (F/) post‐natal (P‐N/) mesenchymal stromal cell (MSC) (called hOssicles [hOss]), which are generated following transplantation CD34 + cells. Serial isolation transplant experiments hMSCs HSPCs hOss revealed dynamic nature hBM niches. modified development by modulating myeloid/lymphoid production HSPC levels, with no major transcriptional changes at single‐cell level. Clonal tracking using genetic barcodes highlighted cross‐talks between endogenous differences clonal myeloid/multipotent F/hOss P‐N/hOss, uncovering ontogeny‐related impact on production.

Language: Английский

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Functional variation among mesenchymal stem cells derived from different tissue sources

PeerJ, Journal Year: 2024, Volume and Issue: 12, P. e17616 - e17616

Published: June 28, 2024

Mesenchymal stem cells (MSCs) are increasingly recognized for their regenerative potential. However, clinical application is hindered by inherent variability, which influenced various factors, such as the tissue source, culture conditions, and passage number. MSCs were sourced from clinically relevant tissues, including adipose tissue-derived (ADMSCs, n = 2), chorionic villi-derived (CMMSCs, amniotic membrane-derived (AMMSCs, 3), umbilical cord-derived (UCMSCs, 3). Passages included cord at P0 (UCMSCP0, P3 (UCMSCP3, P5 (UCMSCP5, 2) well cultured under low-oxygen conditions (UCMSCP5L, 2). We observed that different origins clustered into six distinct functional subpopulations, each with varying proportions. Notably, ADMSCs exhibited a higher proportion of subpopulations associated vascular regeneration, suggesting they beneficial applications in regeneration. Additionally, CMMSCs had high reproductive processes. UCMSCP5 UCMSCP5L proportions related to female function than those earlier passages. Furthermore, UCMSCP5L, (hypoxic) pro-angiogenic characteristics, implications optimizing This study revealed variation distribution MSC among sources, passages, differences functions system These findings hold promise personalized medicine may lead more effective treatments across spectrum medical conditions.

Language: Английский

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Improved therapeutic consistency and efficacy of CD317+ MSCs through stabilizing TSG6 by PTX3

Stem Cell Research & Therapy, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 27, 2024

Abstract Background Previously, we have demonstrated that the batch variations of human platelet lysate (conventional MSC expansion medium) induce heterogeneity and therapeutic inconsistency. On other hand, MSCs expanded with chemical defined medium improved consistency. Methods In current study, studied subpopulation composition variation in different types batches scRNA-seq analysis. Results media higher levels from perspective cell at transcriptome The CD317 + has enhanced immune suppression activities. And percentage within is tightly correlated its activities, also contributes to inconsistency MSCs. increased expression PTX3, which might stabilize TSG6 protein improve effects Conclusions Thus, purifying one efficient strategy reduce increase consistency

Language: Английский

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The Myofibroblast Fate of Therapeutic Mesenchymal Stromal Cells: Regeneration, Repair, or Despair?

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8712 - 8712

Published: Aug. 9, 2024

Mesenchymal stromal cells (MSCs) can be isolated from various tissues of healthy or patient donors to retransplanted in cell therapies. Because the number MSCs obtained biopsies is typically too low for direct clinical application, MSC expansion culture required. However, ex vivo amplification often reduces desired regenerative potential and enhances undesired traits, such as activation into fibrogenic myofibroblasts. Transiently activated myofibroblasts restore tissue integrity after organ injury by producing contracting extracellular matrix scar tissue. In contrast, persistent cause excessive scarring-called fibrosis-that destroys function. this review, we focus on relevance molecular mechanisms myofibroblast upon contact with stiff plastic recipient tissue, hypertrophic scars large skin burns. We discuss mechanoperception integrins stretch-activated channels, mechanotransduction through contractile actin cytoskeleton, conversion mechanical signals transcriptional programs via mechanosensitive co-transcription factors, YAP, TAZ, MRTF. further elaborate how prolonged stress create memory nucleus that evoke lasting epigenetic modifications at DNA level, histone methylation acetylation. conclude projecting mechanics modulated generate MSCs, which epigenetically protected against transport regeneration environment

Language: Английский

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Spatial transcriptomic profiling of human retinoblastoma

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 8, 2024

Abstract Retinoblastoma (RB) represents one of the most prevalent intraocular cancers in children. Understanding tumor heterogeneity RB is important to design better targeted therapies. Here we used spatial transcriptomic profile human retina and comprehensively dissect cell-cell communication networks. We found high intratumoral RB, consisting 10 transcriptionally distinct subpopulations with varying levels proliferation capacity. Our results uncovered a complex architecture microenvironment that predominantly consisted cone precursors, as well glial cells cancer-associated fibroblasts. delineated cell trajectory underlying malignant progression identified key signaling pathways driving genetic regulation across progression. also explored mediating communications subpopulations, mapped networks region neighbors. Altogether, constructed first gene atlas for which allowed us characterize landscape spatially-resolved providing novel insights into involved

Language: Английский

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Humanized in vivo bone marrow models orchestrate multi-lineage human hematopoietic cell development

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 11, 2024

Abstract Hematopoiesis develops in the bone marrow (BM) where multiple interactions regulate differentiation and preservation of hematopoietic stem/progenitor cells (HSPCs). Although murine BM has been extensively analyzed, human microenvironment remains less understood. Immune-deficient models have enabled analysis molecular cellular regulation HSPCs, which limited as develop xenogenic microenvironments. In this study, we thoroughly characterized a humanized (h) vivo model, based on mesenchymal stromal cell (MSC) (called hOssicles (hOss)), compartments generated 3 months post-transplant CD34 + using single-cell RNA sequencing barcoding. Serial isolation MSCs HSPCs from hOss transplant experiments revealed dynamic nature these hBM niches. altered development by modulating myeloid/lymphoid production HSPC levels. Clonal tracking highlighted cross-talks between hOss, indicating multipotent or more restricted lineage origin hematopoiesis shared sites.

Language: Английский

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N-CADHERIN+/CD168- subpopulation determines therapeutic variations of UC-MSCs for cardiac repair after myocardial infarction

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 14, 2024

Background The efficiency of mesenchymal stem cells (MSCs) in treating myocardial infarction (MI) remains inconsistent, which limits their therapeutic applications. Therefore, exploring the mechanism for inconsistent efficacy MSCs and identification criteria screening are important improving MSCs.Methods Mouse model after was utilized to test role from different donor cardiac function. Heterogeneity identified using scRNA-seq MSC-GY, GSEA Scissor analyses were used find functional subpopulations that promote angiogenesis. promoting angiogenesis verified by detecting secretome proteins, ratio N-CADHERIN⁺/CD168⁻ MSCs, tube formation, migration, proliferation HUVECs treatment with conditional medium (CM) derived MSCs.Results We found UC-MSCs donors have varied MI mice higher effectiveness exhibited most potent pro-angiogenic effects secreting elevated levels angiogenesis-related such as MYDGF, VEGFA, FGF2. Single-cell RNA sequencing (scRNA-seq) 10,463 revealed N-cadherin⁺/CD168⁻ subpopulation closely associated effects, this cell positively correlated angiogenic potential MSCs.Conclusions Our study MI, is essential development utilization treatment.

Language: Английский

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