Administration of Adult Human Bone Marrow-Derived, Cultured, Pooled, Allogeneic Mesenchymal Stromal Cells in Critical Limb Ischemia Due to Buerger's Disease: Phase II Study Report Suggests Clinical Efficacy

Gupta, Pawan Kumar; Krishna, Murali; Chullikana, Anoop; Desai, Sanjay C; Murugesan, Ravi Kumar Sabu; Dutta, Sirshak

doi:10.1016/j.jvs.2017.08.009

Cited by 12 publications

(17 citation statements)

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“…These cells are enriched for precursor cells that could be efficacious for therapy [194]. Stempeutics Research's specifications for their allogeneic BMMSC product, Stempeucel, includes parameters such as morphology (fibroblastic and spindle-shaped), cell counts of 180-220 million cells per bag, viability of >85%, ISCT-defined surface marker levels >80% along with CD166 > 80% [71] and CD133 < 5% as their release criteria for administration [195,196]. As more strategies evolve and new criteria are published, the selection panel is continuously being developed.…”

Section: Economic Potential and Market Impact Of Msc Research And Thementioning

confidence: 99%

Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine

Samsonraj

Raghunath

Nurcombe

et al. 2017

Stem Cells Translational Medicine

574

474

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Mesenchymal stem cells (MSC) hold great potential for regenerative medicine because of their ability for self‐renewal and differentiation into tissue‐specific cells such as osteoblasts, chondrocytes, and adipocytes. MSCs orchestrate tissue development, maintenance and repair, and are useful for musculoskeletal regenerative therapies to treat age‐related orthopedic degenerative diseases and other clinical conditions. Importantly, MSCs produce secretory factors that play critical roles in tissue repair that support both engraftment and trophic functions (autocrine and paracrine). The development of uniform protocols for both preparation and characterization of MSCs, including standardized functional assays for evaluation of their biological potential, are critical factors contributing to their clinical utility. Quality control and release criteria for MSCs should include cell surface markers, differentiation potential, and other essential cell parameters. For example, cell surface marker profiles (surfactome), bone‐forming capacities in ectopic and orthotopic models, as well as cell size and granularity, telomere length, senescence status, trophic factor secretion (secretome), and immunomodulation, should be thoroughly assessed to predict MSC utility for regenerative medicine. We propose that these and other functionalities of MSCs should be characterized prior to use in clinical applications as part of comprehensive and uniform guidelines and release criteria for their clinical‐grade production to achieve predictably favorable treatment outcomes for stem cell therapy. Stem Cells Translational Medicine 2017;6:2173–2185

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Section: Economic Potential and Market Impact Of Msc Research And Thementioning

confidence: 99%

Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine

Samsonraj

Raghunath

Nurcombe

et al. 2017

Stem Cells Translational Medicine

574

474

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“…Another concept emerging from meta-analysis is that the response to CD34 + MNCs may be dose-dependent. In support to this hypothesis, treatment of NO-CLI with GCS-Fmobilized-or enriched CD34 + MNCs displayed encouraging results [51,57,58]. Regarding mechanisms, previous studies on CD34 + MNCs showed that they can improve limb reperfusion through extracellular vesicle (EV)-mediated delivery of angiogenic miRNAs [22, 48•, 59, 60•].…”

Section: Mononuclear Cellsmentioning

confidence: 79%

Cell Therapy for Critical Limb Ischemia: Advantages, Limitations, and New Perspectives for Treatment of Patients with Critical Diabetic Vasculopathy

Rampin

Alvino

et al. 2021

Curr Diab Rep

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Purpose of Review To provide a highlight of the current state of cell therapy for the treatment of critical limb ischemia in patients with diabetes. Recent Findings The global incidence of diabetes is constantly growing with consequent challenges for healthcare systems worldwide. In the UK only, NHS costs attributed to diabetic complications, such as peripheral vascular disease, amputation, blindness, renal failure, and stroke, average £10 billion each year, with cost pressure being estimated to get worse. Although giant leaps forward have been registered in the scope of early diagnosis and optimal glycaemic control, an effective treatment for critical limb ischemia is still lacking. The present review aims to provide an update of the ongoing work in the field of regenerative medicine. Recent advancements but also limitations imposed by diabetes on the potential of the approach are addressed. In particular, the review focuses on the perturbation of non-coding RNA networks in progenitor cells and the possibility of using emerging knowledge on molecular mechanisms to design refined protocols for personalized therapy. Summary The field of cell therapy showed rapid progress but has limitations. Significant advances are foreseen in the upcoming years thanks to a better understanding of molecular bottlenecks associated with the metabolic disorders.

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“…Recent clinical studies have demonstrated that the administration of MSCs to patients with CLI is safe (Das et al 2013;Gupta et al 2013Gupta et al , 2017Lasala et al 2011;Lu et al 2011). Given these results and a wealth of encouraging preclinical data, MSCs have become the most clinically relevant CT for testing in CLI patients.…”

Section: Discussionmentioning

confidence: 99%

“…Based on regulatory guidelines, it is recommended that preclinical toxicity and biodistribution assessments using the intended good manufacturing practices (GMP) grade CT product are carried out under good laboratory practices (GLP) prior to submitting an application for clinical testing (US FDA 2013;EMA 2008). It therefore was evident to us that despite the preclinical and clinical data demonstrating safety of human MSCs (hMSCs; Gupta et al 2017;Ramot et al 2009;Guess et al 2017;Creane et al 2017;Yun et al 2016;Schmuck et al 2016;Rengasamy et al 2016;Bura et al 2014;Braun et al 2016;Chen et al 2015;Wang et al 2012;Macisaac et al 2012) that preclinical toxicity and biodistribution studies would be required to assess the safety of our GMP CT product. It was also clear that the product should be administered in a similar manner to the proposed clinical route, which in our case was IM.…”

mentioning

confidence: 99%

A 3-month Safety Assessment of Human Bone Marrow Derived Mesenchymal Stromal Cells Administered Once by the Intramuscular Route to Immunodeficient Mice

et al. 2018

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Critical limb ischemia (CLI) represents the severest manifestation of peripheral arterial disease and is a major unmet medical need. This disease occurs when the arterial blood supply within the limb fails to meet the metabolic demands of the resting muscle or tissue, resulting in chronic ischemic rest pain and/or tissue necrosis. Human mesenchymal stromal cells, termed hMSCs, represent an exciting therapeutic modality for the treatment of this disease due to their immunomodulatory and tissue reparative functions. The aim of the study was to assess the preclinical toxicity profile of human bone marrow-derived MSCs in support of their use as a treatment for CLI. A 3-month toxicity study was carried out under good laboratory practices in immunodeficient mice who received, intramuscularly, a single dose of 3 × 10 (approximately 15 × 10 cells/kg) hMSCs manufactured under good manufacturing practices. No significant changes in body weight, food consumption, clinical signs, or histopathological changes were observed in the hMSC-treated mice in comparison to the controls. These results highlight that the administration of hMSCs during the 3-month study period was well tolerated and not associated with any test item-related tumors. This data set supported the initiation of a phase 1b first in human study in "no option" for revascularization patients with CLI.

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Administration of Adult Human Bone Marrow-Derived, Cultured, Pooled, Allogeneic Mesenchymal Stromal Cells in Critical Limb Ischemia Due to Buerger's Disease: Phase II Study Report Suggests Clinical Efficacy

Cited by 12 publications

References 0 publications

Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine

Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine

Cell Therapy for Critical Limb Ischemia: Advantages, Limitations, and New Perspectives for Treatment of Patients with Critical Diabetic Vasculopathy

A 3-month Safety Assessment of Human Bone Marrow Derived Mesenchymal Stromal Cells Administered Once by the Intramuscular Route to Immunodeficient Mice

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