JOURNAL ARTICLE

Transplantation of mesenchymal cells rejuvenated by the overexpression of telomerase and myocardin promotes revascularization and tissue repair in a murine model of hindlimb ischemia

Rosalinda Madonna, Doris A Taylor, Yong-Jian Geng, Raffaele De Caterina, Harnath Shelat, Emerson C Perin, James T Willerson
Circulation Research 2013 September 13, 113 (7): 902-14
23780385

RATIONALE: The number and function of stem cells decline with aging, reducing the ability of stem cells to contribute to endogenous repair processes. The repair capacity of stem cells in older individuals may be improved by genetically reprogramming the stem cells to exhibit delayed senescence and enhanced regenerative properties.

OBJECTIVE: We examined whether the overexpression of myocardin (MYOCD) and telomerase reverse transcriptase (TERT) enhanced the survival, growth, and myogenic differentiation of mesenchymal stromal cells (MSCs) isolated from adipose or bone marrow tissues of aged mice. We also examined the therapeutic efficacy of transplanted MSCs overexpressing MYOCD and TERT in a murine model of hindlimb ischemia.

METHODS AND RESULTS: MSCs from adipose or bone marrow tissues of young (1 month old) and aged (12 months old) male C57BL/6 and apolipoprotein E-null mice were transiently transduced with lentiviral vectors encoding TERT, MYOCD, or both TERT and MYOCD. Flow cytometry and bromodeoxyuridine cell proliferation assays showed that transduction with TERT and, to a lesser extent, MYOCD, increased MSC viability and proliferation. In colony-forming assays, MSCs overexpressing TERT and MYOCD were more clonogenic than mock-transduced MSCs. Fas-induced apoptosis was inhibited in MSCs overexpressing MYOCD or TERT. When compared with aged mock-transduced MSCs, aged MSCs overexpressing TERT, MYOCD, or both TERT and MYOCD increased myogenic marker expression, blood flow, and arteriogenesis when transplanted into the ischemic hindlimbs of apolipoprotein E-null mice.

CONCLUSIONS: The delivery of the TERT and MYOCD genes into MSCs may have therapeutic applications for restoring, or rejuvenating, aged MSCs from adipose and bone marrow tissues.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
23780385
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"