Unmodified, autologous adipose-derived regenerative cells improve cardiac function, structure and revascularization in a porcine model of chronic myocardial infarction

Abstract

Numerous studies have investigated cell-based therapies for myocardial infarction (MI), with mixed results. In the present study the left anterior descending (LAD) artery of pigs was occluded for 180 min. Four weeks later, the mean left ventricular ejection fraction (LVEF) was shown to have been reduced to approximately 35%. At that time, 18×106 unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) were delivered into the LAD vein (control: delivery of saline). Six weeks following UA-ADRCs/saline delivery, the mean LVEF had increased by 18% (p<0.01) after delivery of UAADRCs, but was unchanged after delivery of saline. This is among the best outcome ever reported in studies on porcine animal models of cell-based therapies for MI in which functional outcome was assessed with cardiac magnetic resonance imaging. The unique combination of the procedure used for isolating UA-ADRCs, the late cell delivery time and the uncommon cell delivery route applied in the present study may open new horizons for cell-based therapies for MI.

Improved guided bone regeneration by combined application of unmodified, fresh autologous adipose derived regenerative cells and plasma rich in growth factors: A first-in-human case report and literature review

“…A study on fresh, uncultured cells that were isolated from adipose tissue of pigs using the Transpose RT system and Matrase Reagent showed that approximately 40% of cells in the stromal vascular fraction were immunopositive for CD29 (thereafter: CD29 + ) and CD44 + [95], which are markers of adipose tissue-derived stem cells[50,96]. Furthermore, on average only 9% of the cells were CD45 + (a marker of blood derived cells[50]), and on average only 11% of the cells were CD31 + (a marker of endothelial cells[50]).…”

Fundamentals of Stem Cells: Why and How Patients' Own Adult Stem Cells Are the Next Generation of Medicine

“…Haenel et al, 2018). Specifically, ADRCs that were isolated with the Matrase enzymatic reagent and the Transpose RT system may contain approximately 40% of cells that are immunopositive for CD29 and CD44, which are markers of ASCs (Haenel et al, 2018). These authors also reported a colony forming units (CFU) frequency (considered to be an indicator of stemness) of approximately 11% of ADRCs isolated with the Matrase enzymatic reagent and the Transpose RT system.…”

“…Isolating ADRCs with the Matrase enzymatic reagent and the Transpose RT system (InGeneron) appears advantagous to other commercial cell separation systems (c.f. Haenel et al, 2018). Specifically, ADRCs that were isolated with the Matrase enzymatic reagent and the Transpose RT system may contain approximately 40% of cells that are immunopositive for CD29 and CD44, which are markers of ASCs (Haenel et al, 2018).…”

“…Fig. 23h and, e.g., Haenel et al, 2018); (vi) positively influence the new host tissue by release of cytokines (among them vascular endothelial growth factor and insulin-like growth factor 1) (Sadat et al, 2007); (vii) protect cells at risk in the new host tissue from undergoing apoptosis (Sadat et al, 2007); and (viii) induce immunemodulatory and anti-inflammatory properties (c.f., e.g., González et al, 2009;Leto Barone et al, 2013), whereby the inhibiting effect on apoptosis may play an important role (Fig. 20).…”

Towards a Comprehensive Understanding of UA-ADRCs (Uncultured, Autologous, Fresh, Unmodified, Adipose Derived Regenerative Cells, Isolated at Point of Care) in Regenerative Medicine

“…Representative, previously unpublished example how autologous, adipose derived stem cells can stay locally, survive and engraft in the new host tissue into which the cells were applied, differentiate under guidance of the new microenvironment, integrate into the new host tissue and participate in building new vascular structures in the host tissue. The panels show photomicrographs of paraffin-embedded, 5 µm thick tissue sections of a post mortem heart from a pig, taken from the left ventricular border zone of myocardial infarction ten weeks after experimental occlusion of the left anterior descending (LAD) artery for three hours, followed by delivery of eGFP-labeled autologous ASCs into the balloon-blocked LAD vein (matching the initial LAD occlusion site) at four weeks after occlusion of the LAD (experiments are described in detail in [111]). (a-e) One tissue section was stained with DAPI (blue) (a) and processed for immunofluorescent detection of GFP (green) (b), von Willebrand factor (vWF) (red) (c) and Troponin (yellow) (d).…”