Newsletter

Drug and Innovation Review

Stem Cell Therapy

Andrew Maslow, MD
Carl Schwartz, MD
Rhode Island Hospital
Providence, RI

Stem cell therapy may offer an alternative therapy for patients with coronary artery disease and ischemic cardiomyopathy^1,2. Benefits include coronary artery angiogenesis, and differentiation into cardiac myocytes. Stem cell therapy may also be a significant source of cells for tissue engineering geared toward the construction of heart valves or other cardiac tissues^1,2.

Stem cells are pluripotent cells that have the ability to differentiate and regenerate into a number of different tissues depending on the local milieu. The stem cells or cell precursors are frequently obtained from the bone marrow, however, cell precurors may also be generated from fatty tissue. Use of stem cells from embryonic bone marrow is limited by ethical concerns, cell rejection, and arrhythmogenicity. Stem cells from autologous bone marrow have similar benefits without the risk of rejection.

Techniques of administration of stem cells include intracoronary injection, intraventricular injection, direct trans-endocardial or epicardial injection, and intravenous injection. Although intravenous injection is simplest, it does not guarantee an adequate delivery of stem cells to the area of concern. Direct injection, which reliably places cells in desired locations, requires more invasive techniques. Intracoronary injection allows direct injection of stem cells to the area of interest without any more risk than that of a cardiac catheterization.

Tissue engineering of cardiac tissues is hoped to provide readily available and durable tissues for the development of cardiac structures. Mesenchymal cells from bone marrow from the sternum of adult sheep have been successfully cultured and grown along a scaffold or skeleton to develop trileaflet heart valves³. Although it is demonstrated that stem cells can be employed for tissue engineering, a number of issues arise including the lack of predictable control of cell growth and proliferation, and the lack of long term data regarding outcome and durability.

The ability to restore cardiac tissue toward its original structure is a significant advancement for the treatment of ischemic heart disease. This is especially important for patients in whom more conventional revascularizations are unlikely to be of benefit or considered too high a risk. In a hypoperfusion heart model, the implantation of stem cell precursors to the left heart reduced the amount of acute injury resulting from coronary occlusion⁴. Increases in vascular endothelial growth factor was recorded along with increases in microvascular density, systolic wall thickening, and systolic segmental wall motion. Authors conclude that implantation of stem cells "is an effective method of inducing therapeutic angiogenisis in the ischemic heart."

Although stem cells are mostly obtained from bone marrow, data show that mesenchymal cells can be isolated from fatty tissue, which can then be regenerated into cardiomyocytes⁵. Cells were treated with 5-azacytidine to stimulate the growth of myocardial tissue. By three weeks the regenerated myocytes began to beat spontaneously in vitro. Myocyte appearance and function was recorded up to 2 months.

The potential for stem cells to offer new therapies for cardiac disease is significant. Pharmacologic therapies are limited by continued progression of disease. Non-pharmacologic treatments including assist devices, pacing techniques, ventricular resection, mechanical hearts, and transplantation are limited by both progression of disease and additional complications pertinent to each procedure. Nevertheless, a number of issues arise with respect to stem cell therapy. These include the lack of long-term outcome data of stem cells, the source of stem cells, the method of administration, and the ability to differentiate to desired cell types. Although still in its infancy, stem cell therapy has the potential to offer regeneration of loss cardiac tissues and restoration of function by using natural tissues.

References

1. Strauer BE, Kornowski R: Stem cell therapy in perspective. Circulation 2003;107:929-934.

2. Gepstein L: Derivation and potential applications of human embryonic stem cells. Circulation Research 2002; 91:866-876.

3. Perry TE, Kaushal S, Suttherland FWH, Guleserian KJ, Bischoff J, Sacks M, Mayer JE: Bone marrow as a cell source for tissue engineering heart valves. Ann Thorac Surg 2003;75:761-767.

4. Nishida M, Li T-S, Hirata K, Yano M, Matsuzaki M, Hamano K: Improvement of cardiac function by bone marrow model. Ann Thorac Surg 2003;75-768:2003.

5. Rangappa S, Fen C, Lee EH, Bongso A, Kwang Wei, ES: Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes. Ann Thorac Surg 2003;75:775-779.

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Table of Contents:

• President's Message
  
  
• Letters to the Editor
  
  
• Drug and Innovation Review
• Intracoronary Brachytherapy
• An Update on Lung Volume Reduction Surgery
• Stem Cell Therapy


• Literature Reviews
• Prevalence of Left Ventricular Diastolic Dysfunction by Doppler Echocardiography: Clinical applications of the Canadian Consensus Guidelines
• Intermittent antegrade warm myocardial protection compared to intermittent cold blood cardioplegia in elective coronary surgery - do we have to change?
• Combined steroid treatment for congenital heart surgery improves oxygen delivery and reduces postbypass inflammatory mediator expression.
• A randomized trial comparing lung-volume-reduction surgery with medical therapy for severe emphysema.
• Nitroprusside in Critically Ill Patients with Left Ventricular Dysfunction and Aortic Stenosis


• Update on American Heart Association
  
  
• Call for Nominations
  
  
• Breakfast Panel at ASA: Hemostatic Balance in Non-Cardiac and Cardiac Surgery Patients
  
  
• Fellow/Faculty Recruitment Reception
  
  
• SCA Research Starter and MidCareer Grants Winners
  
  
• Calendar of Future Meetings

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