Cross talk with hematopoietic cells regulates the endothelial progenitor cell differentiation of CD34 positive cells

• Published in: PloS one 2014-08, Vol.9 (8), p.e106310-e106310
• Main Authors: Kwon, Sang-Mo, Lee, Jun-Hee, Lee, Sang-Hun, Jung, Seok-Yun, Kim, Da-Yeon, Kang, Song-Hwa, Yoo, So-Young, Hong, Jong-Kyu, Park, Ji-Hye, Kim, Jung-Hee, Kim, Sung-Wook, Kim, Yeon-Ju, Lee, Sun-Jin, Kim, Hwi-Gon, Asahara, Takayuki
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Antigens, CD34 - metabolism; Biology; Biology and Life Sciences; Blood flow; Bone marrow; Capillary flow; CD11b antigen; CD3 antigen; CD34 antigen; Cell culture; Cell Differentiation; Cells (biology); Cells, Cultured; Coculture Techniques; Colonies; Comparative analysis; Cord Blood Stem Cell Transplantation; Crosstalk; Differentiation (biology); Disease; Disease Models, Animal; Endothelial Progenitor Cells - cytology; Endothelial Progenitor Cells - physiology; Endothelium; Fetal Blood - cytology; Fetal Blood - metabolism; Hemopoiesis; Hindlimb - blood supply; Human Umbilical Vein Endothelial Cells; Humans; Ischemia; Ischemia - therapy; Laboratories; Leukocyte migration; Lymphocytes; Lymphocytes T; Macrophages; Male; Medical research; Medicine; Megakaryocytes; Mice; Mice, Inbred BALB C; Physiology; Populations; Progenitor cells; Regeneration; Rodents; Stem cells; Therapy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0106310

Despite the crucial role of endothelial progenitor cells (EPCs) in vascular regeneration, the specific interactions between EPCs and hematopoietic cells remain unclear. In EPC colony forming assays, we first demonstrated that the formation of EPC colonies was drastically increased in the coculture of CD34+ and CD34- cells, and determined the optimal concentrations of CD34+ cells and CD34- cells for spindle-shaped EPC differentiation. Functionally, the coculture of CD34+ and CD34- cells resulted in a significant enhancement of adhesion, tube formation, and migration capacity compared with culture of CD34+ cells alone. Furthermore, blood flow recovery and capillary formation were remarkably increased by the coculture of CD34+ and CD34- cells in a murine hind-limb ischemia model. To elucidate further the role of hematopoietic cells in EPC differentiation, we isolated different populations of hematopoietic cells. T lymphocytes (CD3+) markedly accelerated the early EPC status of CD34+ cells, while macrophages (CD11b+) or megakaryocytes (CD41+) specifically promoted large EPC colonies. Our results suggest that specific populations of hematopoietic cells play a role in the EPC differentiation of CD34+ cells, a finding that may aid in the development of a novel cell therapy strategy to overcome the quantitative and qualitative limitations of EPC therapy.