Rationale and design of a randomized controlled trial of allogeneic mesenchymal stem cells in patients with nonischemic cardiomyopathy

Greene, Stephen J.; Epstein, Stephen E.; Kim, Raymond J.; Quyyumi, Arshed A.; Cole, Robert T.; Anderson, Allen S.; Wilcox, Jane E.; Skopicki, Hal A.; Sikora, Sergey; Verkh, Lev; Tankovich, Nikolai; Gheorghiade, Mihai; Butler, Javed

doi:10.2459/jcm.0000000000000303

Cited by 7 publications

(3 citation statements)

References 43 publications

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“…Commercial preparations of DMSO containing cryoprotectants are now widely available and in use for final product formulation in more than 20 cell therapy clinical studies and trials (e.g., NCT00672542 [205], NCT02467387 [206], NCT02166177 [207], NCT01671072 [208], NCT02500849 [209], NCT02208362 [210], NCT02028455 [211], NCT02387723 [212], NCT0212988 [213], (Personal Communication from manufacturers and suppliers of CryStor R [Biolife, STEMCELL Technologies] and CellBanker R [Zenoaq, ASMBio]). However, improved cryoprotectant solutions are urgently needed, in part to address the ever-increasing complexity and di- versity of cell-based products, but also other aspects of regenerative medicine including the preservation of complex tissues and organs.…”

Section: Commercial Development and Regulatory Considerationsmentioning

confidence: 99%

Dimethyl Sulfoxide: A Central Player Since the Dawn of Cryobiology, is Efficacy Balanced by Toxicity?

et al. 2020

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Dimethyl sulfoxide (DMSO) is the cryoprotectant of choice for most animal cell systems since the early history of cryopreservation. It has been used for decades in many thousands of cell transplants. These treatments would not have taken place without suitable sources of DMSO that enabled stable and safe storage of bone marrow and blood cells until needed for transfusion. Nevertheless, its effects on cell biology and apparent toxicity in patients have been an ongoing topic of debate, driving the search for less cytotoxic cryoprotectants. This review seeks to place the toxicity of DMSO in context of its effectiveness. It will also consider means of reducing its toxic effects, the alternatives to its use and their readiness for active use in clinical settings.

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Section: Commercial Development and Regulatory Considerationsmentioning

confidence: 99%

Dimethyl Sulfoxide: A Central Player Since the Dawn of Cryobiology, is Efficacy Balanced by Toxicity?

et al. 2020

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“…An analysis of the literature has shown that only in the last ten years (2012-2023) a large number of clinical studies have been conducted using autologous and allogeneic MSCs for the treatment of diseases such as liver cirrhosis, [30][31][32][33][34][35] cardiomyopathy, [36][37][38][39][40][41][42][43][44] spinal cord injury, [45][46][47][48][49][50] diabetes mellitus. [51][52][53][54][55][56][57][58] Almost all authors note that transplantation, especially of autologous MSCs, is safe and significantly improves the condition of patients.…”

Section: Mscs and Their Application In Preclinical And Clinical Studiesmentioning

confidence: 99%

Freeze‐Dried Mesenchymal Stem Cells: From Bench to Bedside. Review

Paresishvili,

Kakabadze

2023

Advanced Biology

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This review describes the freeze‐dried mesenchymal stem cells (MSCs) and their ability to restore damaged tissues and organs. An analysis of the literature shows that after the lyophilization MSCs retain >80% of paracrine factors and that the mechanism of their action on the restoration of damaged tissues and organs is similar to the mechanism of action of paracrine factors in fresh and cryopreserved mesenchymal stem cells. Based on the own materials, the use of paracrine factors of freeze‐dried MSCs in vivo and in vitro for the treatment of various diseases of organs and tissues has shown to be effective. The study also discusses about the advantages and disadvantages of freeze‐dried MSCs versus cryopreserved MSCs. However, for the effective use of freeze‐dried MSCs in clinical practice, a more detailed study of the mechanism of interaction of paracrine factors of freeze‐dried MSCs with target cells and tissues is required. It is also necessary to identify possible other specific paracrine factors of freeze‐dried MSCs. In addition, develop new therapeutic strategies for the use of freeze‐dried MSCs in regenerative medicine and tissue bioengineering.

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“…For example, nonischemic cardiomyopathy patients with no fibrosis is an example of a clinical model that could be targeted with specific therapies. 27 Clinical models may improve specificity and provide focus on the primary cause and its pathophysiological consequences. This could facilitate mapping of cellular and physiological pathways with the potential for finding unique biomarkers that track when a target and a pathway are engaged.…”

Section: Clinical Modelsmentioning

confidence: 99%

Developing New Treatments for Heart Failure

Gheorghiade

Larson

Shah

et al. 2016

Circ: Heart Failure

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Abstract-Compared with heart failure (HF) care 20 to 30 years ago, there has been tremendous advancement in therapy for ambulatory HF with reduced ejection fraction with the use of agents that block maladaptive neurohormonal pathways. However, during the past decade, with few notable exceptions, the frequency of successful drug development programs has fallen as most novel therapies have failed to offer incremental benefit or raised safety concerns (ie, hypotension). Moreover, no therapy has been approved specifically for HF with preserved ejection fraction or for worsening chronic HF (including acutely decompensated HF). Across the spectrum of HF, preliminary results from many phase II trials have been promising but are frequently followed by unsuccessful phase III studies, highlighting a disconnect in the translational process between basic science discovery, early drug development, and definitive clinical testing in pivotal trials. A major unmet need in HF drug development is the ability to identify homogeneous subsets of patients whose underlying disease is driven by a specific mechanism that can be targeted using a new therapeutic agent. Drug development strategies should increasingly consider therapies that facilitate reverse remodeling by directly targeting the heart itself rather than strictly focusing on agents that unload the heart or target systemic neurohormones. Advancements in cardiac imaging may allow for more focused and direct assessment of drug effects on the heart early in the drug development process. To better understand and address the array of challenges facing current HF drug development, so that future efforts may have a better chance for success, the Food and Drug Administration facilitated a meeting on February 17, 2015, which was attended by clinicians, researchers, regulators, and industry representatives. The following discussion summarizes the key takeaway dialogue from this meeting. Morbidity and mortality for ambulatory patients with heart failure (HF) and reduced ejection fraction (HFrEF) have improved in recent decades through neurohormonal modulation using renin-angiotensin-aldosterone system blockade, β-adrenergic blockade, and most recently, neprilysin inhibition. 1,2 However, despite provision of all available therapies, ambulatory patients with HFrEF continue to have poor long-term outcomes, and with few notable exceptions, successful phase III clinical trials with this population during the past decade have been rare.

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Rationale and design of a randomized controlled trial of allogeneic mesenchymal stem cells in patients with nonischemic cardiomyopathy

Cited by 7 publications

References 43 publications

Dimethyl Sulfoxide: A Central Player Since the Dawn of Cryobiology, is Efficacy Balanced by Toxicity?

Dimethyl Sulfoxide: A Central Player Since the Dawn of Cryobiology, is Efficacy Balanced by Toxicity?

Freeze‐Dried Mesenchymal Stem Cells: From Bench to Bedside. Review

Developing New Treatments for Heart Failure

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