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Ann Thorac Surg 2007;83:1233-1234
© 2007 The Society of Thoracic Surgeons

Correspondence

Cell-Based VEGF Delivery Prevents Donor Cell Apoptosis After Transplantation

Lei Ye, MD, PhDa, Husnain Kh. Haider, MPharm, PhDb, Changfa Guo, MDc, Eugene K.W. Sim, FRCSd

a National University Medical Institutes, National University of Singapore, Singapore, 117597 Singapore
b Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45267-0529
c National University of Singapore, 10 Medical Dr, Singapore, 117597 Singapore
d Department of Surgery, National University of Singapore, Gleneagles JPMC Cardiac Center, Brunei Darussalam, Singapore, 117597 Singapore

(Email: yeleislp{at}hotmail.com; khhaider{at}hotmail.com; g0305832{at}nus.edu.sg; sursimkw{at}nus.edu.sg).

To the Editor:

We read with interest the study by Yau and colleagues [1] that shows vascular endothelial growth factor enhanced survival of transfected skeletal myoblasts and heart cells in the cryo-injured rat heart [1].

The concept of using angiogenic genes to enhance the effects of cell transplant is not new. A combo-therapy approach based on cell and gene therapy improves blood vessel density in and around the infarcted myocardium and restores the left ventricular function of the injured myocardium through neomyogenesis [2–4]. We have shown that transplantation of vascular endothelial growth factor-165 (VEGF165) transfected human skeletal myoblasts resulted in increased neovascularization and regional blood flow with improvement of heart function in a pig heart model [2]. Furthermore we have shown that myoblast carrying both VEGF165 and angiopoietin-1 genes had greater neovascularization in ischemically injured limbs [5].

Host immune unrelated mechanisms including mechanical injury, ischemic stress, and host tissue inflammatory response have been implicated in the extensive donor cell death after transplantation. A strategy that may help the donor cells to defy the biochemically unfavorable host tissue environment and enhance their survival would give better prognosis after heart cell therapy. The VEGF, like other growth factors, has been shown to activate phosphatidylinositol-3 kinase and phosphorylation of protein kinase B (PKB) that is important signaling pathway for cell survival. Hence, the transient overexpression of VEGF in the donor cells is expected to enhance their survival.

The present study by Yau and colleagues [1] has shown extensive survival of cells from an allogenic source in an immunocompetent host with the presence of elevated VEGF levels at the site of cell grafting. The authors have reported the total number of donor-derived cells based on rat "Y" chromosomal quantitative polymerase chain reaction (PCR). This number would include the surviving cells as well as proliferating cells, which may not be a reflection of the surviving cells. Suzuki and colleagues [6] estimated surviving cell number by 14C-label. Serial time study from 10 minutes, 24 hours, and 72 hours showed steady decreases to 7.9 ± 0.6% of surviving cells by 14C-label, whereas the total cell number increased to 24.4 ± 1.6% at 72 hours as detected by the Smcy gene. Our experience [7] with xenotransplantation of human skeletal myoblasts in a rat heart model of myocardial infarction has shown increase in the total cell number with time based on "Y" chromosomal specific real time PCR. Hence there is a need for cautious interpretation of the results while using a single method for quantification of cell survival posttransplantation. Furthermore, important details that would interest the readers, such as the purity of skeletal myoblasts, are not included and this would be of importance as it would influence cell survival rate. Such details would further enhance the importance of this article.


   References
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 References
 

  1. Yau TM, Kim C, Ng D, et al. Increasing transplanted cell survival with cell-based angiogenic gene therapy Ann Thorac Surg 2005;80:1779-1786.[Abstract/Free Full Text]
  2. Kh Haider H, Ye L, Jiang SJ, et al. Angiomyogenesis for cardiac repair using human myoblasts as carriers of human vascular endothelial growth factor J Mol Med 2004;82:539-549.[Medline]
  3. Ye L, Kh Haider H, Jiang SJ, et al. Reversal of myocardial injury using genetically modulated human skeletal myoblasts in a rodent cryoinjured heart model Eur J Heart Fail 2005;7:945-952.[Abstract/Free Full Text]
  4. Suzuki K, Murtuza B, Smolenski RT, et al. Cell transplantation for the treatment of acute myocardial infarction using vascular endothelial growth factor–expressing skeletal myoblasts Circulation 2001;104:I207-I212.[Medline]
  5. Niagara MI, Kh Haider H, Ye L, et al. Autologous skeletal myoblasts transduced with a new adenoviral bicistronic vector for treatment of hind limb ischemia J Vasc Surg 2004;40:774-785.[Medline]
  6. Suzuki K, Murtuza B, Beauchamp JR, et al. Role of interleukin-1ß in acute inflammation and graft death after cell transplantation to the heart Circulation 2004;10:II219-II224.
  7. Guo CF, Kh Haider H, Ye L, et al. Human myoblasts are immunoprivileged and enhanced by cyclosporine treatment with improvement of heart function after xenogenic transplantation for cardiac repair Ann Acad Med Singapore 2005;34:S227.

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Terrence M. Yau, Angelo DeGasperis, and Lorenza DeGasperis
Ann. Thorac. Surg. 2007 83: 1234. [Extract] [Full Text] [PDF]



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Ann. Thorac. Surg., March 1, 2007; 83(3): 1234 - 1234.
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