Am J Cardiovasc Dis 2012;2(1):58-67
Review Article
c-kit-positive cardiac stem cells and myocardial regeneration
Toru Hosoda
Tokai University Institute of Innovative Science and Technology, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan
Received November 15, 2011; accepted December 2, 2011; Epub December 15, 2011; Published January 1, 2011
Abstract: Two distinct subpopulations of endogenous cardiac stem cells (CSCs) are identified in the adult heart; myogenic
CSCs (mCSCs), which are characterized by the presence of c-kit receptor, reside in the myocyte niche surrounded by
matured cardiomyocytes, whereas vasculogenic CSCs (vCSCs), which express c-kit as well as KDR, are stored in the
vascular niche found in the vessel wall. They both possess the fundamental properties of stem cells: self-renewing,
clonogenic, and multipotent. While mCSCs preferentially differentiate into myocyte lineage in vitro, vCSCs tend to commit to
vascular endothelial or smooth muscle lineages upon stimulation. Intramyocardial injection of human mCSCs to the
region bordering infarct of immunosuppressed animals induces cardiac regeneration involving intensive muscle and
vessel formation. On the other hand, the administration of human vCSCs near the critical stenosis created in the dog
coronary artery results in the formation of large conductive vessels, i.e. “biological coronary bypass”, coupled with the
improved tissue perfusion. A clinical trial utilizing autologous c-kit-positive CSCs on patients with chronic ischemic heart
failure was launched recently. Upon coronary artery bypass graft (CABG) surgery, a small portion of the right atrial
appendage was obtained and used for isolation and expansion of CSCs. Intracoronary CSC implantation was performed 4
months after the surgery, and the symptom and the cardiac function were followed. Although the study is still ongoing, no
adverse event due to cell infusion has been reported in any of the cell-treated patients, and the initial outcome is very
promising. Disease-based customized cell therapy employing various combinations of autologous mCSCs and vCSCs
would become available in the near future. (AJCD1111002).
Keywords: Cardiac stem cells, c-kit, myocardial regeneration, heart failure
Full Text PDF
Address all correspondence to:
Toru Hosoda, MD, PhD
Tokai University Institute of Innovative Science and Technology,
143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan
Phone: +81-463-93-1121 (ext. 2784); Fax: +81-463-95-3522
E-mail: hosoda@tokai-u.jp
Review Article
c-kit-positive cardiac stem cells and myocardial regeneration
Toru Hosoda
Tokai University Institute of Innovative Science and Technology, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan
Received November 15, 2011; accepted December 2, 2011; Epub December 15, 2011; Published January 1, 2011
Abstract: Two distinct subpopulations of endogenous cardiac stem cells (CSCs) are identified in the adult heart; myogenic
CSCs (mCSCs), which are characterized by the presence of c-kit receptor, reside in the myocyte niche surrounded by
matured cardiomyocytes, whereas vasculogenic CSCs (vCSCs), which express c-kit as well as KDR, are stored in the
vascular niche found in the vessel wall. They both possess the fundamental properties of stem cells: self-renewing,
clonogenic, and multipotent. While mCSCs preferentially differentiate into myocyte lineage in vitro, vCSCs tend to commit to
vascular endothelial or smooth muscle lineages upon stimulation. Intramyocardial injection of human mCSCs to the
region bordering infarct of immunosuppressed animals induces cardiac regeneration involving intensive muscle and
vessel formation. On the other hand, the administration of human vCSCs near the critical stenosis created in the dog
coronary artery results in the formation of large conductive vessels, i.e. “biological coronary bypass”, coupled with the
improved tissue perfusion. A clinical trial utilizing autologous c-kit-positive CSCs on patients with chronic ischemic heart
failure was launched recently. Upon coronary artery bypass graft (CABG) surgery, a small portion of the right atrial
appendage was obtained and used for isolation and expansion of CSCs. Intracoronary CSC implantation was performed 4
months after the surgery, and the symptom and the cardiac function were followed. Although the study is still ongoing, no
adverse event due to cell infusion has been reported in any of the cell-treated patients, and the initial outcome is very
promising. Disease-based customized cell therapy employing various combinations of autologous mCSCs and vCSCs
would become available in the near future. (AJCD1111002).
Keywords: Cardiac stem cells, c-kit, myocardial regeneration, heart failure
Full Text PDF
Address all correspondence to:
Toru Hosoda, MD, PhD
Tokai University Institute of Innovative Science and Technology,
143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan
Phone: +81-463-93-1121 (ext. 2784); Fax: +81-463-95-3522
E-mail: hosoda@tokai-u.jp
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