Title
CD34+ cells home, proliferate, and participate in capillary formation, and in combination with CD34- cells enhance tube formation in a 3-dimensional matrix
Author
Rookmaaker, M.B.
Verhaar, M.C.
Loomans, C.J.M.
Verloop, R.
Peters, E.
Westerweel, P.E.
Murohara, T.
Staal, F.J.T.
van Zonneveld, A.J.
Koolwijk, P.
Rabelink, T.J.
van Hinsbergh, V.W.M.
TNO Kwaliteit van Leven
Publication year
2005
Abstract
Objective - Emerging evidence suggests that human blood contains bone marrow (BM)-derived endothelial progenitor cells that contribute to postnatal neovascularization. Clinical trials demonstrated that administration of BM-cells can enhance neovascularization. Most studies, however, used crude cell populations. Identifying the role of different cell populations is important for developing improved cellular therapies. Methods and Results - Effects of the hematopoietic stem cell-containing CD34+ cell population on migration, proliferation, differentiation, stimulation of, and participation in capillary-like tubule formation were assessed in an in vitro 3-dimensional matrix model using human microvascular endothelial cells. During movement over the endothelial monolayer, CD34+ cells remained stuck at sites of capillary tube formation and time- and dose-dependently formed cell clusters. Immunohistochemistry confirmed homing and proliferation of CD34+ cells in and around capillary sprouts. CD34+ cells were transduced with the LNGFR marker gene to allow tracing. LNGFR gene-transduced CD34 + cells integrated in the tubular structures and stained positive for CD31 and UEA-1. CD34+ cells alone stimulated neovascularization by 17%. Coculture with CD34- cells led to 68% enhancement of neovascularization, whereas CD34- cells displayed a variable response by themselves. Cell-cell contact between CD34+ and CD34- cells facilitated endothelial differentiation of CD34+ cells. Conclusions - Our data suggest that administration of CD34+-enriched cell populations may significantly improve neovascularization and point at an important supportive role for (endogenous or exogenous) CD34- cells. © 2005 American Heart Association, Inc. Chemicals / CAS: nitric oxide, 10102-43-9; Antigens, CD34; Biological Markers
Subject
Biology
Biomedical Research
Angiogenesis
Gene therapy
Nitric oxide, endothelium, vascular type
CD34 antigen
Nitric oxide
Bone marrow cell
Capillary endothelium
Capillary proliferation
Cell population
Cell proliferation
Facilitation
Gene therapy
Hhematopoietic stem cell
Human cell
Immunohistochemistry
Marker gene
Neovascularization (pathology)
Nerve sprouting
Neural tube
Peripheral vascular disease
Antigens, CD34
Biological Markers
Capillaries
Cell Differentiation
Cell Division
Cell Movement
Cell Separation
Cells, Cultured
Coculture Techniques
Endothelium, Vascular
Fetal Blood
Hematopoietic Stem Cells
Humans
Neovascularization, Physiologic
To reference this document use:
http://resolver.tudelft.nl/uuid:c494ef0e-39c3-4de4-a1c4-855463414953
DOI
https://doi.org/10.1161/01.atv.0000177808.92494.14
TNO identifier
238685
ISSN
1079-5642
Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 25 (9), 1843-1850
Document type
article