Concise Review: Is Cardiac Cell Therapy Dead? Embarrassing Trial Outcomes and New Directions for the Future

Tang, Jun; Cores, Jhon; Huang, Ke; Cui, Xiaolin; Luo, Lan; Zhang, Jin Ying; Li, Tao‐Sheng; Li, Qian; Cheng, Ke

doi:10.1002/sctm.17-0196

Cited by 104 publications

(87 citation statements)

References 78 publications

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“…6c-h). We and others have demonstrated that the cell-free secretome derived from stem cells can achieve a level of protection and regeneration similar or superior to the cells themselves 4,[26][27][28][29] . Our observations showed that LSC-Sec was capable of reversing fibrosis caused by Bleo or silica particles (Figs.…”

Section: Discussionmentioning

confidence: 98%

Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis

et al. 2020

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Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable form of interstitial lung disease in which persistent injury results in scar tissue formation. As fibrosis thickens, the lung tissue loses the ability to facilitate gas exchange and provide cells with needed oxygen. Currently, IPF has few treatment options and no effective therapies, aside from lung transplant. Here we present a series of studies utilizing lung spheroid cell-secretome (LSC-Sec) and exosomes (LSC-Exo) by inhalation to treat different models of lung injury and fibrosis. Analysis reveals that LSC-Sec and LSC-Exo treatments could attenuate and resolve bleomycin-and silica-induced fibrosis by reestablishing normal alveolar structure and decreasing both collagen accumulation and myofibroblast proliferation. Additionally, LSC-Sec and LSC-Exo exhibit superior therapeutic benefits than their counterparts derived from mesenchymal stem cells in some measures. We showed that an inhalation treatment of secretome and exosome exhibited therapeutic potential for lung regeneration in two experimental models of pulmonary fibrosis.

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Section: Discussionmentioning

confidence: 98%

Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis

et al. 2020

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“…Thus, MSCs may target both systemic inflammation and the cardiac pathological changes associated with HFpEF. However, MSC therapy in cardiovascular disease remains of unclear utility, owing to the limited results from relatively small clinical trials, as well as an incomplete understanding of their mechanism of action [46,47].…”

Section: Introductionmentioning

confidence: 99%

Immune Dysregulation in HFpEF: A Target for Mesenchymal Stem/Stromal Cell Therapy

Sava

Pepine

March

2020

JCM

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Over 26 million people worldwide suffer from heart failure, a disease associated with a 1 year mortality rate of 22%. Half of these patients present heart failure with preserved ejection fraction (HFpEF), for which there is no available therapy to improve prognosis. HFpEF is strongly associated with aging, inflammation, and comorbid burden, which are thought to play causal roles in disease development. Mesenchymal stromal/stem cells (MSCs) have potent immunomodulatory actions and promote tissue healing, thus representing an attractive therapeutic option in HFpEF. In this review, we summarize recent data suggesting that a two-hit model of immune dysregulation lies at the heart of the HFpEF. A first hit is represented by genetic mutations associated with clonal hematopoiesis of indeterminate potential (CHIP), which skew immune cells toward a pro-inflammatory phenotype, are associated with HFpEF development in animal models, and with immune dysregulation and risk of HF hospitalization in patients. A second hit is induced by cardiovascular risk factors, which cause subclinical cardiac dysfunction and production of danger signals. In mice, these attract proinflammatory macrophages, Th1 and Th17 cells into the myocardium, where they are required for the development of HFpEF. MSCs have been shown to reduce the pro-inflammatory activity of immune cell types involved in murine HFpEF in vitro, and to reduce myocardial fibrosis and improve diastolic function in vivo, thus they may efficiently target immune dysregulation in HFpEF and stop disease progression.

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“…Notably, the ALLSTAR study (allogenic intracoronary CDCs injected <6 month after MI; http://clinicaltrials.gov: NCT01458405) was abandoned as an interim analysis of data from 142 patients demonstrated a low probability (futility) of achieving a statistically significant difference in the 12‐month primary efficacy endpoint (i.e., relative improvement in infarct size from baseline) . Although this outcome was attributed to unforeseen improvements in the placebo arm (i.e., natural history of the disease) and technical variability seen in the scar measurements by the steering committee, these data highlight the need to maximize indirect (paracrine) repair by heart‐derived cell therapies if clinical translation is to have any hope for success .…”

Section: Heart‐derived Stem Cellsmentioning

confidence: 99%

Concise Review: Heart-Derived Cell Therapy 2.0: Paracrine Strategies to Increase Therapeutic Repair of Injured Myocardium

Rafatian

Davis

2018

Stem Cells

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Despite progress in cardiovascular medicine, the incidence of heart failure is rising and represents a growing challenge. To address this, ex vivo proliferated heart-derived cell products have emerged as a promising investigational cell-treatment option. Despite being originally proposed as a straightforward myocyte replacement strategy, emerging evidence has shown that cell-mediated gains in cardiac function are leveraged on paracrine stimulation of endogenous repair and tissue salvage. In this concise review, we focus on the paracrine repertoire of heart-derived cells and outline strategies used to boost cell potency by targeting cytokines, metabolic preconditioning and supportive biomaterials. Mechanistic insights from these studies will shape future efforts to use defined factors and/or synthetic cell approaches to help the millions of patients worldwide suffering from heart failure. Stem Cells 2018.

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Concise Review: Is Cardiac Cell Therapy Dead? Embarrassing Trial Outcomes and New Directions for the Future

Cited by 104 publications

References 78 publications

Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis

Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis

Immune Dysregulation in HFpEF: A Target for Mesenchymal Stem/Stromal Cell Therapy

Concise Review: Heart-Derived Cell Therapy 2.0: Paracrine Strategies to Increase Therapeutic Repair of Injured Myocardium

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