First-in-Man Study of a Cardiac Extracellular Matrix Hydrogel in Early and Late Myocardial Infarction Patients

Traverse, Jay H.; Henry, Timothy D.; Dib, Nabil; Patel, Amit N.; Pepine, Carl J.; Schaer, Gary L.; DeQuach, Jessica A.; Kinsey, Adam M.; Chamberlin, Paul; Christman, Karen L.

doi:10.1016/j.jacbts.2019.07.012

Cited by 225 publications

(213 citation statements)

References 36 publications

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“…The MM hydrogel was shown to increase cardiac muscle and improve cardiac function in preclinical MI models [6][7][8][9] . A Phase I clinical trial was also completed with this material 3 using transendocardial injections in post-MI patients, which supported the safety and feasibility of this approach (ClinicalTrials.gov Identifier: NCT02305602) 14 . However, direct tissue injections in patients require delayed delivery because of acute risks related to ventricular rupture and arrythmias 3,15 while cardiomyocyte death and negative left ventricular (LV) remodeling are processes that commence within minutes to days after the MI.…”

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confidence: 81%

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Healing Tissues From the Inside Out: Infusible Biomaterial for Targeting and Treating Inflammatory Tissues via Intravascular Administration

Spang

Lazerson

Bhatia

et al. 2020

Preprint

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Extracellular matrix (ECM) hydrogels have been widely used in preclinical studies as injectable materials for tissue engineering therapies. We have developed a new ECM therapy, the soluble fraction derived from decellularized, digested ECM, for intravascular infusion. This new form of ECM is capable of gelation in vivo and can be delivered acutely after an injury to promote cell survival and improve vascularization. In this study, we show proof-of-concept for the feasibility, safety, and efficacy of ECM infusions using small and large animal models of acute myocardial infarction (MI) and intracoronary infusion. Following infusion, the ECM material was retained in the heart, specifically in regions of ischemia, and colocalized with endothelial cells, coating the leaky microvasculature. Functional improvements, specifically reduced left ventricular volumes, were observed after ECM infusion post-MI. Genes associated with angiogenesis were upregulated, and genes associated with cell apoptosis/necrosis and fibrosis were downregulated. The ECM was also delivered using a clinically-relevant catheter in a large animal model of acute MI. This study shows proof-of-concept for a new intravascular delivery strategy for ECM biomaterial therapies with potential implications for a variety of pathologies with ischemic tissue or injured vasculature.

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confidence: 81%

“…The MM hydrogel was selected as a starting material for its demonstrated efficacy in preclinical models [6][7][8][9]18 and translational proof-of-concept in a Phase I clinical trial 14 . MM hydrogel was generated based on previously described protocols (Fig 1).…”

Section: Soluble Extracellular Matrix Hydrogel Can Be Isolated and Ismentioning

confidence: 99%

Healing Tissues From the Inside Out: Infusible Biomaterial for Targeting and Treating Inflammatory Tissues via Intravascular Administration

Spang

Lazerson

Bhatia

et al. 2020

Preprint

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“…The proposed therapies entailed the transplantation of CPCs or the application of human induced pluripotent stem cells (hiPSCs), mainly delivered through cell injections (Bartunek et al, 2017;Butler et al, 2017), cell-matrix inoculation (Traverse et al, 2019;U.S. National Library of Medicine, 2019a), cell sheets (Miyagawa et al, 2017) and cell patches (Dolan et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Combining Nanomaterials and Developmental Pathways to Design New Treatments for Cardiac Regeneration: The Pulsing Heart of Advanced Therapies

Cassani

Fernandes

Vrbský

et al. 2020

Front. Bioeng. Biotechnol.

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Cassani et al. Nanoparticles for Heart Regeneration function are some of the main achievements reached so far by nanoparticle-based treatments in animal models. This work offers an overview on the recent nanomedical applications for cardiac regeneration and highlights how the versatility of nanomaterials can be combined with the newest molecular biology discoveries to advance cardiac regeneration therapies.

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“…Amongst these alternative therapies, a decellularized myocardial matrix hydrogel derived from left ventricular porcine tissue has been demonstrated as a post-MI therapy leading to mitigation of negative left ventricular remodeling and loss of function in small and large animal models compared to controls 15,16 , leading to evaluation in a Phase I clinical trial 17 . Notably, analysis of the matrix treated tissue provided evidence suggesting some promotion of mechanisms to restore the cardiomyocyte population.…”

Section: Introductionmentioning

confidence: 99%

Myocardial matrix material supports a proliferative microenvironment for cardiomyocytes

Wang

Cattaneo

Luo

et al. 2020

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Novel therapeutics have sought to stimulate the endogenous repair mechanisms in the mammalian myocardium as the native regenerative potential of the adult cardiac tissue is limited. In particular, a myocardial matrix derived injectable hydrogel has shown efficacy and safety in various animal myocardial infarction (MI) including evidence of increased myocardium. In this study, investigation on the properties of this myocardial matrix material demonstrated its native capability as an effective reactive oxygen species (ROS) scavenger that can protect against oxidative stress and maintain cardiomyocyte proliferation in vitro. In vivo assessment of of myocardial matrix hydrogel treatment post-MI demonstrated increased thymidine analog uptake in cardiomyocytes compared to saline controls along with co-staining with cell cycle progression marker, phospho-histone H3. Overall, this study provides further evidence that properties of the myocardial matrix hydrogel promote an environment supportive of cardiomyocytes undergoing cell cycle progression.

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First-in-Man Study of a Cardiac Extracellular Matrix Hydrogel in Early and Late Myocardial Infarction Patients

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Cited by 225 publications

References 36 publications

Healing Tissues From the Inside Out: Infusible Biomaterial for Targeting and Treating Inflammatory Tissues via Intravascular Administration

Healing Tissues From the Inside Out: Infusible Biomaterial for Targeting and Treating Inflammatory Tissues via Intravascular Administration

Combining Nanomaterials and Developmental Pathways to Design New Treatments for Cardiac Regeneration: The Pulsing Heart of Advanced Therapies

Myocardial matrix material supports a proliferative microenvironment for cardiomyocytes

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