Mesenchymal Stromal Cells in the Clinic: What Do the Clinical Trials Say?

2012 ◽  
pp. 423-433
Author(s):  
Vivek Tanavde ◽  
Mohan C. Vemuri
Keyword(s):  
Clinical Trials ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells

Use of autologous bone marrow mesenchymal stromal cells for cartilage repair clinical trials

Cytotherapy ◽  
2013 ◽  
Vol 15 (4) ◽  
pp. S45
Author(s):  
P. Law ◽  
L. Wong ◽  
F. Wong ◽  
S. Tan ◽  
Y. Liew ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Trials ◽  
Mesenchymal Stromal Cells ◽  
Cartilage Repair ◽  
Stromal Cells ◽  
Autologous Bone Marrow ◽  
Autologous Bone

scholarly journals Mesenchymal stromal cells: a novel therapy for the treatment of chronic obstructive pulmonary disease?

Thorax ◽  
2018 ◽  
Vol 73 (6) ◽  
pp. 565-574 ◽  
Author(s):  
Winifred Broekman ◽  
Padmini P S J Khedoe ◽  
Koen Schepers ◽  
Helene Roelofs ◽  
Jan Stolk ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Animal Studies ◽  
Chronic Obstructive ◽  
Tissue Destruction ◽  
Novel Therapy ◽  
Model Studies

COPD is characterised by tissue destruction and inflammation. Given the lack of curative treatments and the progressive nature of the disease, new treatments for COPD are highly relevant. In vitro cell culture and animal studies have demonstrated that mesenchymal stromal cells (MSCs) have the capacity to modify immune responses and to enhance tissue repair. These properties of MSCs provided a rationale to investigate their potential for treatment of a variety of diseases, including COPD. Preclinical models support the hypothesis that MSCs may have clinical efficacy in COPD. However, although clinical trials have demonstrated the safety of MSC treatment, thus far they have not provided evidence for MSC efficacy in the treatment of COPD. In this review, we discuss the rationale for MSC-based cell therapy in COPD, the main findings from in vitro and in vivo preclinical COPD model studies, clinical trials in patients with COPD and directions for further research.

scholarly journals When Origin Matters: Properties of Mesenchymal Stromal Cells From Different Sources for Clinical Translation in Kidney Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Sandra Calcat-i-Cervera ◽  
Clara Sanz-Nogués ◽  
Timothy O'Brien
Keyword(s):  
Cell Culture ◽  
Clinical Trials ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Scale Up ◽  
Clinical Translation ◽  
Health Concern ◽  
Optimal Scale ◽  
Wide Range ◽  
Processing Variables

Advanced therapy medicinal products (ATMPs) offer new prospects to improve the treatment of conditions with unmet medical needs. Kidney diseases are a current major health concern with an increasing global prevalence. Chronic renal failure appears after many years of impairment, which opens a temporary window to apply novel therapeutic approaches to delay or halt disease progression. The immunomodulatory, anti-inflammatory, and pro-regenerative properties of mesenchymal stromal cells (MSCs) have sparked interest for their use in cell-based regenerative therapies. Currently, several early-phase clinical trials have been completed and many are ongoing to explore MSC safety and efficacy in a wide range of nephropathies. However, one of the current roadblocks to the clinical translation of MSC therapies relates to the lack of standardization and harmonization of MSC manufacturing protocols, which currently hinders inter-study comparability. Studies have shown that cell culture processing variables can have significant effects on MSC phenotype and functionality, and these are highly variable across laboratories. In addition, heterogeneity within MSC populations is another obstacle. Furthermore, MSCs may be isolated from several sources which adds another variable to the comparative assessment of outcomes. There is now a growing body of literature highlighting unique and distinctive properties of MSCs according to the tissue origin, and that characteristics such as donor, age, sex and underlying medical conditions may alter the therapeutic effect of MSCs. These variables must be taken into consideration when developing a cell therapy product. Having an optimal scale-up strategy for MSC manufacturing is critical for ensuring product quality while minimizing costs and time of production, as well as avoiding potential risks. Ideally, optimal scale-up strategies must be carefully considered and identified during the early stages of development, as making changes later in the bioprocess workflow will require re-optimization and validation, which may have a significant long-term impact on the cost of the therapy. This article provides a summary of important cell culture processing variables to consider in the scale-up of MSC manufacturing as well as giving a comprehensive review of tissue of origin-specific biological characteristics of MSCs and their use in current clinical trials in a range of renal pathologies.

scholarly journals Comparison of Single and Repeated Dosing of Anti-Inflammatory Human Umbilical Cord Mesenchymal Stromal Cells in a Mouse Model of Polymicrobial Sepsis

2021 ◽  
Author(s):  
Barbara Fazekas ◽  
Senthilkumar Alagesan ◽  
Luke Watson ◽  
Olivia Ng ◽  
Callum M. Conroy ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Single Dose ◽  
Umbilical Cord ◽  
Mesenchymal Stromal Cells ◽  
Inflammatory Mediators ◽  
Stromal Cells ◽  
Response To Therapy ◽  
Polymicrobial Sepsis ◽  
Human Umbilical Cord ◽  
Cell Subpopulations

Abstract Mesenchymal stromal cells (MSCs) ameliorate pre-clinical sepsis and sepsis-associated acute kidney injury (SA-AKI) but clinical trials of single-dose MSCs have not indicated robust efficacy. This study investigated immunomodulatory effects of a novel MSC product (CD362-selected human umbilical cord-derived MSCs [hUC-MSCs]) in mouse endotoxemia and polymicrobial sepsis models.Initially, mice received intra-peritoneal (i.p.) lipopolysaccharide (LPS) followed by single i.p. doses of hUC-MSCs or vehicle. Next, mice underwent cecal ligation and puncture (CLP) followed by intravenous (i.v.) doses of hUC-MSCs at 4 hours or 4 and 28 hours. Analyses included serum/plasma assays of biochemical indices, inflammatory mediators and the AKI biomarker NGAL; multi-color flow cytometry of peritoneal macrophages (LPS) and intra-renal immune cell subpopulations (CLP) and histology/immunohistochemistry of kidney (CLP).At 72 hours post-LPS injections, hUC-MSCs reduced serum inflammatory mediators and peritoneal macrophage M1/M2 ratio. Repeated, but not single, hUC-MSC doses administered at 48 hours post-CLP resulted in increased survival, lower serum concentrations of inflammatory mediators, lower plasma NGAL and reversal of sepsis-associated depletion of intra-renal T-cell and myeloid cell subpopulations. Hierarchical clustering analysis of all 48-hour serum/plasma analytes demonstrated partial co-clustering of repeated-dose hUC-MSC CLP animals with a Sham group but did not reveal a distinct signature of response to therapy. It was concluded that repeated doses of CD362-selected hUC-MSCs are required to modulate systemic and local immune/inflammatory events in polymicrobial sepsis and SA-AKI. Inter-individual variability and lack of effect of single dose MSC administration in the CLP model are consistent with observations to date from early-phase clinical trials.

scholarly journals Immunological Characterization Of Multipotent Mesenchymal Stromal Cells. The International Society For Cellular Therapy (ISCT) Working Proposal

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5438-5438
Author(s):  
Mauro Krampera ◽  
Jacques Galipeau ◽  
Yufang Shi ◽  
Karin Tarte ◽  
Luc Sensebé
Keyword(s):  
Clinical Trials ◽  
Mesenchymal Stromal Cells ◽  
International Society ◽  
Stromal Cells ◽  
Quantitative Methods ◽  
Multipotent Mesenchymal Stromal Cells ◽  
In Vivo Models ◽  
Immunological Characterization

Abstract The large number of experimental approaches, culture conditions, qualitative and quantitative methods, and in vitro and in vivo models employed so far to assess immune regulatory properties of multipotent mesenchymal stromal cells (MSC) has led to an excess of literature data that sometimes are poorly comparable, redundant, and even contradictory. Thus, quite paradoxically, the risk is that pre-clinical literature data may become eventually weak and scarcely useful, in both researchers’ and Regulatory Authorities’ opinion, for supporting experimentally specific MSC-based clinical trials aimed at treating autoimmune and inflammatory diseases. However, some data in this field appear more solid and reproducible and may be generally accepted to suggest reproducible immunological assays to quantify the differences in immune modulatory properties of MSCs produced according to Good Manufacturing Practice (GMP). The MSC Committee of the International Society of Cell Therapy (ISCT) released a statement paper in 2006 that established the minimal criteria characterizing human MSC, without focusing particularly on their immunological properties. In the 7 years following the publication of this statement paper, more than 10,000 manuscripts on MSC, and many of them deal with immune regulation. To consolidate the scientific research in this field, the MSC Committee of the ISCT is publishing a working proposal paper aimed at stimulating the general discussion about the need of shared guidelines for the immunological characterization of MSCs for clinical use: 1. A standard immune plasticity assay should be implemented by using IFN-γ + TNF-α as model in vitro priming agent 2. Functional analysis of an expanded cell product may provide mechanistic insights on intra- and inter- study variance in clinical response amongst patients 3. The use of purified responders would be widely practicable and should provide more generalizable guidance on relative functional potency of MSC and as a companion to clinical trials 4. Interrogating the IDO response as part of an in vitro licensing assay should be considered central 5. Conclusions based on xenorecipient animal models on how to conduct clinical trials should be drawn with caution 6. The prospective hypothesis-driven analysis of lymphocyte populations in patients groups treated with MSC should be encouraged 7. Clinical analysis should also include the monitoring of whether injected MSCs are the target of an immune response. Disclosures: No relevant conflicts of interest to declare.

scholarly journals In utero treatment of myelomeningocele with placental mesenchymal stromal cells — Selection of an optimal cell line in preparation for clinical trials

2020 ◽  
Vol 55 (9) ◽  
pp. 1941-1946 ◽  
Author(s):  
Laura A Galganski ◽  
Priyadarsini Kumar ◽  
Melissa A Vanover ◽  
Christopher D Pivetti ◽  
Jamie E Anderson ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cell Line ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
In Utero ◽  
Selection Of

scholarly journals Challenges and advances in clinical applications of mesenchymal stromal cells

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tian Zhou ◽  
Zenan Yuan ◽  
Jianyu Weng ◽  
Duanqing Pei ◽  
Xin Du ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Clinical Applications ◽  
Disease Models ◽  
Animal Disease ◽  
Animal Disease Models

AbstractMesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, have been intensely investigated for clinical applications within the last decades. However, the majority of registered clinical trials applying MSC therapy for diverse human diseases have fallen short of expectations, despite the encouraging pre-clinical outcomes in varied animal disease models. This can be attributable to inconsistent criteria for MSCs identity across studies and their inherited heterogeneity. Nowadays, with the emergence of advanced biological techniques and substantial improvements in bio-engineered materials, strategies have been developed to overcome clinical challenges in MSC application. Here in this review, we will discuss the major challenges of MSC therapies in clinical application, the factors impacting the diversity of MSCs, the potential approaches that modify MSC products with the highest therapeutic potential, and finally the usage of MSCs for COVID-19 pandemic disease.

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