Epicardial transplantation of atrial appendage micrograft patch salvages myocardium after infarction

Abstract

BACKGROUND: Ischemic heart disease remains the leading cause of mortality and morbidity worldwide despite improved possibilities in medical care. Alongside interventional therapies, such as coronary artery bypass grafting, adjuvant tissue-engineered and cell-based treatments can provide regenerative improvement. Unfortunately, most of these advanced approaches require multiple lengthy and costly preparation stages without delivering significant clinical benefits. METHODS: We evaluated the effect of epicardially delivered minute pieces of atrial appendage tissue material, defined as atrial appendage micrografts (AAMs), in a mouse myocardial infarction model. An extracellular matrix patch was used to cover and fix the AAMs onto the surface of the infarcted heart. RESULTS: The matrix-covered AAMs salvaged the heart from the infarction-induced loss of functional myocardium and attenuated scarring. Site-selective proteomics of injured ischemic and uninjured distal myocardium from AAMs-treated and -untreated tissue sections revealed increased expression of several cardiac regeneration-associated proteins (i.e., periostin, transglutaminases, and glutathione peroxidases) and activation of pathways responsible for angiogenesis and cardiogenesis in relation to AAMs therapy. CONCLUSIONS: Epicardial delivery of AAMs encased in an extracellular matrix patch scaffold salvages functional cardiac tissue from ischemic injury and restricts fibrosis after myocardial infarction. Our results support the use of AAMs as tissue-based therapy adjuvants for salvaging the ischemic myocardium.

A Novel Autologous Micrografts Technology in Combination with Negative Pressure Wound Therapy (NPWT) for Quick Granulation Tissue Formation in Chronic/Refractory Ulcer

“…In vitro studies have shown that mechanically obtained micrografts are enriched with mesenchymal progenitor cells, growth factors, and extracellular matrix components [19,23]. The technology has been successfully applied in different clinical contexts: dentistry field [13], dermatology for androgenetic alopecia [9,24], traumatology for chondropathy [14], osteonecrosis [15], and cardiology field for cardiac ischemia [16]. Our present result demonstrated that micrografts helped a severe intractable wound to generate qualified granulation tissue.…”

“…Looking back at its history, this particular micrografts technology started with hair-containing punched tissues [9], and since then, different tissues have been subjected: skin [10], dermis [11], fat [12], periosteum [13], cartilage [14], bone [15], and atrial appendage [16]. The grafts may contain by themselves resident cells, progenitor cells, as well as various tissue factors including cytokines and growth factors.…”

Epitranscriptomics of Ischemic Heart Disease—The IHD-EPITRAN Study Design and Objectives

“…The right atrial appendage (RAA) is often manipulated during cardiac surgery to assemble bypass circulation. Moreover, RAA has been evaluated as a safe source for cardiac tissue for both diagnostic and therapeutic applications [ 115 ]. During the IHD-EPITRAN, a small RAA tissue sample, the size of which will be guided by clinical characteristics, will be collected from the study participants in cohorts II and III to enable an organ-specific characterization of the RNA epitranscriptomes ( Figure 4 ).…”

Autologous cardiac micrografts as support therapy to coronary artery bypass surgery

“…We recently reported AAMs transplantation to improve the myocardium structurally and functionally after ischemic damage in a mouse model. 11 The multidisciplinary AADC consortium has successfully provided the leverage to translate these findings into clinical application initially as a clinical case report and description of methodology 10 and now here into the clinical safety and feasibility evaluation in support to CABG surgery. These results have thus paved the way for a more extensive further assessment of AAMs transplantation in terms of efficacy and safety, again relying on the wide cross-disciplinary expertise of AADC consortium partners.…”

“…7, 8, 9 To this end, we have demonstrated the preclinical efficacy and initial clinical feasibility 10 of autologous cardiac microtissue, atrial appendage micrografts (AAMs), and have shown that AAMs therapy activates cardiogenic and cardioprotective pathways. 11 Based on these encouraging results, we initiated a phase I open-label, non- randomized clinical study 12 to evaluate the safety and feasibility of AAMs transplantation in conjunction with CABG surgery. We utilized gadolinium-enhanced cardiac magnetic resonance (CMR) imaging before and six months after treatment to gain detailed insight into the AAMs ‘efficacy to induce myocardial repair.…”