Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Oct 26, 2019; 11(10): 831-858
Published online Oct 26, 2019. doi: 10.4252/wjsc.v11.i10.831
Unmodified autologous stem cells at point of care for chronic myocardial infarction
Alexander Haenel, Mohamad Ghosn, Tahereh Karimi, Jody Vykoukal, Dipan Shah, Miguel Valderrabano, Daryl G Schulz, Albert Raizner, Christoph Schmitz, Eckhard U Alt
Alexander Haenel, Tahereh Karimi, Eckhard U Alt, Heart and Vascular Institute, Department of Medicine, Tulane University Health Science Center, New Orleans, LA 70112, United States
Alexander Haenel, Daryl G Schulz, Eckhard U Alt, The Methodist Hospital Research Institute, Houston, TX 77030, United States
Alexander Haenel, Department of Radiology and Nuclear Medicine, University Hospital Schleswig-Holstein, Lübeck D-23562, Germany
Mohamad Ghosn, Dipan Shah, Miguel Valderrabano, Albert Raizner, Houston Methodist DeBakey Heart and Vascular Center, Houston, TX 77030, United States
Jody Vykoukal, Department of Translational Molecular Pathology, MD Anderson Cancer Center, The University of Texas, Houston, TX 77030, United States
Christoph Schmitz, Institute of Anatomy, Faculty of Medicine, LMU Munich, Munich D-80336, Germany
Eckhard U Alt, Isar Klinikum Munich, Munich D-80331, Germany
Author contributions: Raizner A and Alt EU substantially contributed to conception and design of the study; Haenel A, Ghosn M, Karimi T, Vykoukal J, Shah D, Valderrabano M, Schulz DG, Raizner A and Alt EU substantially contributed to acquisition of data; Haenel A, Ghosn M, Karimi T, Vykoukal J, Shah D, Schulz DG, Raizner A, Schmitz C and Alt EU substantially contributed to analysis and interpretation of data; Haenel A, Schmitz C and Alt EU drafted the article; Haenel A, Raizner A, Schmitz C and Alt EU made critical revisions related to important intellectual content of the manuscript; All authors approved the version of the article to be published.
Supported by Alliance of Cardiovascular Researchers (New Orleans, LA 70102, United States), No. 2013-AH-01 (to Haenel A)
Institutional review board statement: This study was approved by the Institutional Review Board of Houston Methodist Hospital (Houston, TX, United States).
Institutional animal care and use committee statement: The animal use protocol has been reviewed and approved by the Institutional Animal Care and Use Committee at Houston Methodist Hospital (Houston, TX, United States) (AUP-0910-0019).
Conflict-of-interest statement: Schmitz C has served as consultant of SciCoTec (Grünwald, Germany), the principal shareholder of InGeneron, Inc. (Houston, TX, United States). Alt EU is Chairman of the Board of Isar Klinikum and of InGeneron, Inc.
Data sharing statement: Requests for access to data should be addressed to the corresponding author.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Eckhard U Alt, MD, PhD, Professor of Medicine, Heart and Vascular Institute, Department of Medicine, Tulane University, Health Science Center, 1340 Tulane Ave., New Orleans, LA 70112, United States.
Telephone: +1-504-9883040
Received: February 18, 2019
Peer-review started: February 20, 2019
First decision: April 15, 2019
Revised: June 5, 2019
Accepted: August 26, 2019
Article in press: August 26, 2019
Published online: October 26, 2019

Numerous studies investigated cell-based therapies for myocardial infarction (MI). The conflicting results of these studies have established the need for developing innovative approaches for applying cell-based therapy for MI. Experimental studies on animal models demonstrated the potential of fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) for treating acute MI. In contrast, studies on the treatment of chronic MI (CMI; > 4 wk post-MI) with UA-ADRCs have not been published so far. Among several methods for delivering cells to the myocardium, retrograde delivery into a temporarily blocked coronary vein has recently been demonstrated as an effective option.


To test the hypothesis that in experimentally-induced chronic myocardial infarction (CMI; > 4 wk post-MI) in pigs, retrograde delivery of fresh, uncultured, unmodified, autologous adipose-derived regenerative cells (UA-ADRCs) into a temporarily blocked coronary vein improves cardiac function and structure.


The left anterior descending (LAD) coronary artery of pigs was blocked for 180 min at time point T0. Then, either 18 × 106 UA-ADRCs prepared at “point of care” or saline as control were retrogradely delivered via an over-the-wire balloon catheter placed in the temporarily blocked LAD vein 4 wk after T0 (T1). Effects of cells or saline were assessed by cardiac magnetic resonance (CMR) imaging, late gadolinium enhancement CMR imaging, and post mortem histologic analysis 10 wk after T0 (T2).


Unlike the delivery of saline, delivery of UA-ADRCs demonstrated statistically significant improvements in cardiac function and structure at T2 compared to T1 (all values given as mean ± SE): Increased mean LVEF (UA-ADRCs group: 34.3% ± 2.9% at T1 vs 40.4 ± 2.6% at T2, P = 0.037; saline group: 37.8% ± 2.6% at T1 vs 36.2% ± 2.4% at T2, P > 0.999), increased mean cardiac output (UA-ADRCs group: 2.7 ± 0.2 L/min at T1 vs 3.8 ± 0.2 L/min at T2, P = 0.002; saline group: 3.4 ± 0.3 L/min at T1 vs 3.6 ± 0.3 L/min at T2, P = 0.798), increased mean mass of the left ventricle (UA-ADRCs group: 55.3 ± 5.0 g at T1 vs 71.3 ± 4.5 g at T2, P < 0.001; saline group: 63.2 ± 3.4 g at T1 vs 68.4 ± 4.0 g at T2, P = 0.321) and reduced mean relative amount of scar volume of the left ventricular wall (UA-ADRCs group: 20.9% ± 2.3% at T1 vs 16.6% ± 1.2% at T2, P = 0.042; saline group: 17.6% ± 1.4% at T1 vs 22.7% ± 1.8% at T2, P = 0.022).


Retrograde cell delivery of UA-ADRCs in a porcine model for the study of CMI significantly improved myocardial function, increased myocardial mass and reduced the formation of scar tissue.

Keywords: Adipose tissue-derived regenerative cells, Chronic myocardial infarction, Heart failure, Stem cells, Translational medicine, Point of care cell therapy

Core tip: We report results derived from a feasibility study on pigs whose left anterior descending artery was occluded for 180 min. Four weeks later, 18 × 106 fresh, uncultured, unmodified, autologous adipose-derived regenerative cells were retrogradely delivered into the balloon-blocked left anterior descending vein (control: delivery of saline). Another 6 wk later, the mean left ventricular mass (+29%; P < 0.001) and cardiac output (+37%; P = 0.002) had significantly increased after cell delivery. The unique combination of the procedure used for isolating stem cells and the novel cell delivery route applied in the present study potentially opens new horizons for clinical therapy for chronic myocardial infarction.