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Transient Inhibition of Transforming Growth Factor-beta 1 in Human Diabetic CD34(+) Cells Enhances Vascular Reparative Functions

  1. Author:
    Bhatwadekar, A. D.
    Guerin, E. P.
    Jarajapu, Y. P. R.
    Caballero, S.
    Sheridan, C.
    Kent, D.
    Kennedy, L.
    Lansang, M. C.
    Ruscetti, F. W.
    Pepine, C. J.
    Higgins, P. J.
    Bartelmez, S. H.
    Grant, M. B.

  2. Author Address

    [Kennedy, Laurence; Lansang, M. Cecilia; Grant, Maria B.] Univ Florida, Div Endocrinol Diabet & Metab, Gainesville, FL 32611 USA. [Pepine, Carl J.] Univ Florida, Div Cardiol, Gainesville, FL USA. [Guerin, E. P.; Kent, David] Vis Clin, Kilkenny, Ireland. [Sheridan, Carl] Univ Liverpool, Sch Clin Sci, Liverpool L69 3BX, Merseyside, England. [Ruscetti, Frank W.] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21701 USA. [Higgins, Paul J.] Albany Med Coll, Ctr Cell Biol & Canc Res, Albany, NY 12208 USA. [Bartelmez, Stephen H.] BetaStem Therapeut Inc, San Francisco, CA USA.;Grant, MB, Univ Florida, Div Endocrinol Diabet & Metab, Gainesville, FL 32611 USA.
    1. Year: 2010
    2. Date: Aug
  2. Journal: Diabetes
    1. 59
    2. 8
    3. Pages: 2010-2019
  4. Type of Article: Article
  5. ISSN: 0012-1797
  1. Abstract:

    OBJECTIVE-Peripheral blood CD34(+) cells from diabetic patients demonstrate reduced vascular reparative function due to decreased proliferation and diminished migratory prowess, largely resulting from decreased nitric oxide (NO) bioavailability. The level of TGF-beta, a key factor that modulates stem cell quiescence, is increased in the serum of type 2 diabetic patients We asked whether transient TGF-beta 1 inhibition in CD34(+) cells would improve their reparative ability. RESEARCH DESIGN AND METHODS-To inhibit TGF-beta 1 protein expression, CD34(+) cells were treated ex vivo with antisense phosphorodiamidate morpholino oligomers (TGF-beta 1-PMOs) and analyzed for cell surface CXCR4 expression, cell survival in the absence of added growth factors, SDF-1-induced migration, NO release, and in vivo retinal vascular reparative ability. RESULTS-TGF-beta 1-PMO treatment of diabetic CD34(+) cells resulted in increased expression of CXCR4, enhanced survival in the absence of growth factors, and increased migration and NO release as compared with cells treated with control PMO Using a retinal ischemia reperfusion injury model in mice, we observed that recruitment of diabetic CD34(+) cells to injured acellular retinal capillaries was greater after TGF-beta 1-PMO treatment compared with control PMO-treated cells. CONCLUSIONS-Transient inhibition of TGF-beta 1 may represent a promising therapeutic strategy for restoring the reparative capacity of dysfunctional diabetic CD34(+) cells. Diabetes 59:2010-2019, 2010

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External Sources

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  2. DOI: 10.2337/db10-0287
  3. View record in Web of Science®
  4. WOS: 000280749100020

Library Notes

  1. Fiscal Year: FY2009-2010
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