Adipose Tissue-Derived Cells Improve Cardiac Function Following Myocardial Infarction

Schenke-Layland, Katja; Strem, Brian M.; Jordan, Maria C.; DeEmedio, Michael T.; Hedrick, Marc H.; Roos, Kenneth P.; Fraser, John K.; MacLellan, W. Robb

doi:10.1016/j.jss.2008.03.019

« Previous Next »Journal of Surgical Research
Volume 153, Issue 2 , Pages 217-223, 15 May 2009

Adipose Tissue-Derived Cells Improve Cardiac Function Following Myocardial Infarction1

Katja Schenke-Layland, Ph.D.
- Cardiovascular Research Laboratory, Departments of Medicine and Physiology, David Geffen School of Medicine at the University of California-Los Angeles (UCLA), Los Angeles, California
Brian M. Strem, Ph.D.
- Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles (UCLA), Los Angeles, California
- Cytori Therapeutics, Inc. San Diego, California
Maria C. Jordan, M.D.
- Cardiovascular Research Laboratory, Departments of Medicine and Physiology, David Geffen School of Medicine at the University of California-Los Angeles (UCLA), Los Angeles, California
Michael T. DeEmedio, B.S.
- Cytori Therapeutics, Inc. San Diego, California
Marc H. Hedrick, M.D.
- Department of Surgery, David Geffen School of Medicine at University of California-Los Angeles (UCLA), Los Angeles, California
- Cytori Therapeutics, Inc. San Diego, California
Kenneth P. Roos, Ph.D.
- Cardiovascular Research Laboratory, Departments of Medicine and Physiology, David Geffen School of Medicine at the University of California-Los Angeles (UCLA), Los Angeles, California
John K. Fraser, Ph.D.
- Cytori Therapeutics, Inc. San Diego, California
W. Robb MacLellan, M.D.
- Cardiovascular Research Laboratory, Departments of Medicine and Physiology, David Geffen School of Medicine at the University of California-Los Angeles (UCLA), Los Angeles, California
- To whom correspondence and reprint requests should be addressed at the Cardiovascular Research Laboratory, David Geffen School of Medicine at UCLA, 675 C. E. Young Drive, MRL 3-645, Los Angeles, California, 90095-1760

Received 10 January 2008 published online 12 May 2008.

Background

Adipose tissue consists of mature adipocytes and a mononuclear cell fraction termed adipose tissue-derived cells (ADCs). Within these heterogeneous ADCs exists a mesenchymal stem cell-like cell population, termed adipose tissue-derived stem cells. An important clinical advantage of adipose tissue-derived stem cells over other mesenchymal stem cell populations is the fact that they can be isolated in real time in sufficient quantity, such that ex vivo expansion is not necessary to obtain clinically relevant numbers for various therapeutic applications.

Materials and methods

The aim of this investigation was to evaluate the therapeutic potential of freshly isolated ADCs in treating rats acutely following myocardial infarction. Rats underwent 45 min of left anterior descending artery occlusion followed by reperfusion. Fifteen minutes post-myocardial infarction, saline or 5 × 10⁶ ADCs from green fluorescent protein-expressing transgenic rats were injected into the chamber of the left ventricle. Left ventricular function and morphometry was followed with 2-D echocardiography for 12 wk, at which point hearts were harvested for histological analysis.

Results

Twelve weeks following cell therapy, left ventricular end-diastolic dimension was less dilated while the ejection fraction and cardiac output of ADC-treated rats were significantly improved compared to control rats (P < 0.01). Despite this benefit, absolute engraftment rates were low. This paradox may be partially explained by ADC-induced increases in both capillary and arteriole densities.

Conclusions

These data confirm the therapeutic benefit of freshly isolated ADCs delivered post-MI and suggest a novel beneficial mechanism for ADCs through a potent proangiogenic effect.

Key Words: myocardial infarction, cell transplantation, stem cells, cardiac function