PMID- 20443864 OWN - NLM STAT- MEDLINE DCOM- 20100730 LR - 20240324 IS - 1752-8062 (Electronic) IS - 1752-8054 (Print) IS - 1752-8054 (Linking) VI - 2 IP - 1 DP - 2009 Feb TI - c-Kit+ bone marrow stem cells differentiate into functional cardiac myocytes. PG - 26-32 LID - 10.1111/j.1752-8062.2008.00089.x [doi] AB - The utility of bone marrow cells (BMCs) to regenerate cardiac myocytes is controversial. The present study examined the capacity of different types of BMCs to generate functional cardiac myocytes. Isolated c-kit(+) BMCs (BMSCs), c-kit(+) and crude BMCs from the adult feline femur were membrane stained with PKH26 dye or infected with a control enhanced green fluorescence protein transcript (EGFP)-adenovirus prior to co-culture upon neonatal rat ventricular myocytes (NRVM). Co-cultured cells were immuno-stained for c-kit, alpha-tropomyosin, alpha-actinin, connexin 43 (Cx43) and Ki67 and analyzed with confocal microscopy. Electrophysiology of BMSC derived myocytes were compared to NRVMs within the same culture dish. Gap junction function was analyzed by fluorescence recovery after photo-bleaching (FRAP). BMCs proliferated and differentiated into cardiac myocytes during the first 48 hours of co-culturing. These newly formed cardiac myocytes were able to contract spontaneously or synchronously with neighboring NRVMs. The myogenic rate of c-kit(+) BMSCs was significantly greater than c-kit(+) and crude BMCs (41.2 +/- 2.1, 6.1 +/- 1.2, and 17.1 +/- 1.5%, respectively). The newly formed cardiac myocytes exhibited an immature electrophysiological phenotype until they became electrically coupled to NRVMs through functional gap junctions. BMSCs did not become functional myocytes in the absence of NRVMs. In conclusion, c-kit(+) BMSCs have the ability to transdifferentiate into functional cardiac myocytes. FAU - Kubo, Hajime AU - Kubo H AD - Department of Physiology, Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA, USA. FAU - Berretta, Remus M AU - Berretta RM FAU - Jaleel, Naser AU - Jaleel N FAU - Angert, David AU - Angert D FAU - Houser, Steven R AU - Houser SR LA - eng GR - P01 HL108806/HL/NHLBI NIH HHS/United States GR - R01 HL033921/HL/NHLBI NIH HHS/United States GR - R0133921/PHS HHS/United States GR - R01 HL089312/HL/NHLBI NIH HHS/United States GR - P01 HL091799/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Clin Transl Sci JT - Clinical and translational science JID - 101474067 RN - 0 (Contractile Proteins) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit) SB - IM MH - Animals MH - Animals, Newborn MH - Bone Marrow Cells/*cytology MH - Cats MH - Cell Communication MH - Cell Cycle MH - *Cell Differentiation MH - Cell Proliferation MH - Coculture Techniques MH - Contractile Proteins/metabolism MH - Electrophysiological Phenomena MH - Fluorescence Recovery After Photobleaching MH - Gap Junctions/metabolism MH - Heart Ventricles/cytology MH - Myocardial Contraction/physiology MH - Myocytes, Cardiac/*cytology/metabolism MH - Proto-Oncogene Proteins c-kit/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Sarcomeres/metabolism MH - Stem Cells/*cytology/*metabolism PMC - PMC4122301 MID - NIHMS446732 EDAT- 2009/02/01 00:00 MHDA- 2010/07/31 06:00 PMCR- 2009/02/01 CRDT- 2010/05/07 06:00 PHST- 2010/05/07 06:00 [entrez] PHST- 2009/02/01 00:00 [pubmed] PHST- 2010/07/31 06:00 [medline] PHST- 2009/02/01 00:00 [pmc-release] AID - CTS089 [pii] AID - 10.1111/j.1752-8062.2008.00089.x [doi] PST - ppublish SO - Clin Transl Sci. 2009 Feb;2(1):26-32. doi: 10.1111/j.1752-8062.2008.00089.x.