Skip to main content

Advertisement

Log in

Endothelial-pericyte interactions in angiogenesis

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract.

It takes two to make blood vessels—endothelial cells and pericytes. While the endothelial cells are the better characterized of the two, pericytes are now coming into focus as important regulators of angiogenesis and blood vessel function, and as potential drug targets. However, pericytes are still surrounded by much controversy. They are difficult to define, they constitute a heterogeneous population of cells, and their ontogeny is not well understood. They are plastic and have the capacity to differentiate into other mesenchymal cell types, such as smooth muscle cells, fibroblasts and osteoblasts. Recent interest in pericytes also stems from their potential involvement in diseases such as diabetic microangiopathy, tissue fibrosis, cancer, atherosclerosis and Alzheimer's disease. The present review focuses on the role of pericytes in physiological angiogenesis. The currently favored view states that the initial endothelial tubes form without pericyte contact, and that subsequent acquisition of pericyte coverage leads to vessel remodeling, maturation and stabilization. Improved means of identifying and visualizing pericytes now challenge this view and show that high numbers of pericytes invest in actively sprouting and remodeling vessels. Genetic data demonstrate the critical importance of pericytes for vascular morphogenesis and function, and imply specific roles for the cell type in various aspects of angiogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1a–h.

Similar content being viewed by others

References

  • Abramsson A, Berlin Ö, Papayan H, Paulin D, Shani M, Betsholtz C (2002) Analysis of mural cell recruitment to tumor vessels. Circulation 105:112–117

    CAS  PubMed  Google Scholar 

  • Allt G, Lawrenson JG (2001) Pericytes: cell biology and pathology. Cells Tissues Organs 169:1–11

    Article  CAS  PubMed  Google Scholar 

  • Amselgruber WM, Schafer M, Sinowatz F (1999) Angiogenesis in the bovine corpus luteum: an immunocytochemical and ultrastructural study. Anat Histol Embryol 28:157–166

    Article  CAS  PubMed  Google Scholar 

  • Antonelli-Orlidge A, Saunders KB, Smith SR, D'Amore PA (1989) An activated form of TGF-beta is produced by co-cultures of endothelial cells and pericytes. Proc Natl Acad Sci U S A 86:4544–4548

    CAS  PubMed  Google Scholar 

  • Balabanov R, Dore-Duffy P (1998) Role of the CNS microvascular pericyte in the blood-brain barrier. J Neurosci Res 53:637–644

    Article  CAS  PubMed  Google Scholar 

  • Balabanov R, Beaumont T, Dore-Duffy P (1999) Role of central nervous system microvascular pericytes in activation of antigen-primed splenic T lymphocytes. J Neurosci Res 55:578–587

    Article  CAS  PubMed  Google Scholar 

  • Benjamin LE, Hemo I, Keshet E (1998) A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Development 125:1591–1598

    CAS  PubMed  Google Scholar 

  • Benjamin LE, Golijanin D, Itin A, Pode D, Keshet E (1999) Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. J Clin Invest 103:159–165

    CAS  PubMed  Google Scholar 

  • Bergwerff M, Verberne ME, DeRuiter MC, Poelmann RE, Gittenbergerde Groot AC (1998) Neural crest cell contribution to the developing circulatory system: implications for vascular morphology? Circ Res 82:221–231

    Google Scholar 

  • Betsholtz C, Karlsson L, Lindahl P (2001) Developmental roles of platelet derived growth factors. Bioessays 23:494–507

    Article  CAS  PubMed  Google Scholar 

  • Bondjers C, Kalén M, Hellström M, Scheidl SJ, Abramsson A, Renner O, Lindahl P, Cho H, Kehrl J, Betsholtz C (2003) Transcription profiling of PDGF-B deficient embryos identifies RGS5 as a novel marker for pericytes and vascular smooth muscle cells. Am J Pathol 162:721–729

    CAS  PubMed  Google Scholar 

  • Buetow BS, Crosby JR, Kaminski WE, Ramachandran RK, Lindahl P, Martin P, Betsholtz C, Seifert RA, Raines EW, Bowen-Pope DF (2001) PDGF-B chain of hematopoietic origin is not necessary for granulation tissue formation and its absence enhances vascularization. Am J Pathol (in press)

  • Carmeliet P, Mackman N, Moons L, Luther T, Gressens P, Van Vlaenderen I, Demunck H, Kasper M, Breier G, Evrard P, et al. (1996) Role of tissue factor in embryonic blood vessel development. Nature 383:73–75

    CAS  PubMed  Google Scholar 

  • Carmeliet P, Ng YS, Nuyens D, Theilmeier G, Brusselmans K, Cornelissen I, Ehler E, Kakkar VV, Stalmans I, Mattot V, et al. (1999) Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188. Nat Med 5:495–502

    Article  CAS  PubMed  Google Scholar 

  • Cho H, Kozaka T, Bondjers C, Betsholtz C, Kehrl J (2003) Pericyte specific expression of RGS5: implications for PDGF and EDG receptor signaling during vascular maturation. FASEB J 17:440–442

    CAS  PubMed  Google Scholar 

  • Courtoy PJ, Boyles J (1983) Fibronectin in the microvasculature: localization in the pericyte-endothelial interstitium. J Ultrastruct Res 83:258–273

    CAS  PubMed  Google Scholar 

  • Crosby JR, Seifert RA, Soriano P, Bowen-Pope DF (1998) Chimaeric analysis reveals role of Pdgf receptors in all muscle lineages. Nat Genet 18:385–388

    CAS  PubMed  Google Scholar 

  • Cuevas P, Gutierrez-Diaz JA, Reimers D, Dujovny M, Diaz FG, Ausman JI (1984) Pericyte endothelial gap junctions in human cerebral capillaries. Anat Embryol 170:155–159

    CAS  PubMed  Google Scholar 

  • D'Amore PA (1997) Capillary growth: a two-cell system. Semin Cancer Biol 3:49–56

    Google Scholar 

  • DeRuiter MC, Poelmann RE, VanMunsteren JC, Mironov V, Markwald RR, Gittenberger-de Groot AC (1997) Embryonic endothelial cells transdifferentiate into mesenchymal cells expressing smooth muscle actins in vivo and in vitro. Circ Res 80:444–451

    CAS  PubMed  Google Scholar 

  • Diaz-Flores L, Gutierrez R, Varela N, Rancel F, Valladares F (1991) Microvascular pericytes: a review of their morphological and functional characteristics. Histol Histopathol 6:269–286

    CAS  PubMed  Google Scholar 

  • Diaz-Flores L, Gutierrez R, Lopez-Alonso A, Gonzales R, Varela H (1992) Pericytes as a supplementary source of osteoblasts in periosteal osteogenesis. Clin Orthop 275:280–286

    PubMed  Google Scholar 

  • Dickson MC, Martin JS, Cousins FM, Kulkarni AB, Karlsson S, Akhurst RJ (1995) Defective haematopoiesis and vasculogenesis in transformin growth factor beta-1 knock-out mice. Development 121:1845–1854

    CAS  PubMed  Google Scholar 

  • Doherty MJ, Canfield AE (2000) Gene expression during vascular pericyte differentiation. Crit Rev Eukaryot Gene Expr 9:1–17

    Google Scholar 

  • Dor Y, Djonov V, Abramovitch R, Itin A, Fishman GI, Goelman G, Keshet E (2002) Conditional switching of VEGF provides new insights into adult neovascularization and pro-angiogenic therapy. EMBO J 21:1939–1947

    Article  CAS  PubMed  Google Scholar 

  • Drake CJ, Hungerford JE, Little CD (1998) Morphogenesis of the first blood vessels. Ann N Y Acad Sci 857:155–179

    CAS  PubMed  Google Scholar 

  • Ema M, Faloon P, Zhang WJ, Hirashima M, Reid T, Stanford WL, Orkin S, Choi K, Rossant J (2003) Combinatorial effects of Flk1 and Tal1 on vascular and hematopoietic development in the mouse. Genes Dev 17:380–393

    Article  CAS  PubMed  Google Scholar 

  • Enge M, Bjarnegård M, Gerhardt H, Gustafsson E, Kalén M, Asker N, Hammes H-P, Shani M, Fässler R, Betsholtz C (2002) Endothelium specific platelet-derived growth factor-B ablation mimics diabetic retinopathy. EMBO J 21:4307–4316

    Article  CAS  PubMed  Google Scholar 

  • Enge M, Wilhelmsson U, Abramsson A, Stakeberg J, Kühn R, Betsholtz C, Pekny M (2003) Neuron-specific ablation of PDGF-B is compatible with normal central nervous system development and astroglial response to injury. Neurochem Res 28:271–279

    Article  CAS  PubMed  Google Scholar 

  • Etchevers HC, Couly GF, Le Douarin NM (2002) Morphogenesis of the branchial vascular sector. Trends Cardiovasc Med 12:299–304

    Article  PubMed  Google Scholar 

  • Fruttiger M (2002) Development of the mouse retinal vasculature: angiogenesis versus vasculogenesis. Invest Ophthalmol Vis Sci 43:522–527

    PubMed  Google Scholar 

  • Gee MS, Procopio WN, Makonnen S, Feldman MD, Yeilding NM, Lee WMF (2003) Tumor vessel development and maturation impose limits on the effectiveness of anti-vascular therapy. Am J Pathol 162:183–193

    PubMed  Google Scholar 

  • Gerhardt H, Wolburg H, Redies C (2000) N-cadherin mediates pericytic endothelial interaction during brain angiogenesis in the chicken. Dev Dyn 218:472–479

    CAS  PubMed  Google Scholar 

  • Goumans M-J, Valdimarsdottir G, Itoh S, Rosendahl A, Sideras P, ten Dijke P (2002) Balancing the activation state of the endothelium via two distinct TGF-β type I receptors. EMBO J 21:1743–1753

    Article  CAS  PubMed  Google Scholar 

  • Hammes H-P, Lin J, Renner O, Shani M, Lundqvist A, Betsholtz C, Brownlee M, Deutsch U (2002) Pericytes and the pathogenesis of diabetic retinopathy. Diabetes 51:3107–3112

    CAS  PubMed  Google Scholar 

  • Hellström M, Kalén M, Lindahl P, Abramsson A, Betsholtz C (1999) Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development 126:3047–3055

    CAS  PubMed  Google Scholar 

  • Hellström M, Gerhardt H, Kalén M, Li X, Eriksson U, Wolburg H, Betsholtz C (2001) Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J Cell Biol 153:543–553

    PubMed  Google Scholar 

  • Hirschi KK, Rohovsky SA, Beck LH, Smith SR, D'Amore PA (1999) Endothelial cells modulate the proliferation of mural cell precursors via platelet-derived growth factor-BB and heterotypic cell contact. Circ Res 84:298–305

    CAS  PubMed  Google Scholar 

  • Hungerford JE, Little CD (1999) Developmental biology of the vascular smooth muscle cell: building a multilayered vessel wall. J Vasc Res 36:2–27

    Article  CAS  PubMed  Google Scholar 

  • Joyce NC, DeCamilli P, Lohmann SM, Walter U (1986) cGMP dependent protein kinase is present in high concentrations in contractile cells of the kidney vasculature. J Cyclic Nucleotide Protein Phosphor Res 11:191–198

    CAS  PubMed  Google Scholar 

  • Kaminski W, Lindahl P, Lin NL, Broudy VC, Crosby JR, Swolin B, Bowen-Pope DF, Martin P, Ross R, Betsholtz C, Raines EW (2001) The basis of hematopoietic defects in PDGF-B and PDGFRbeta deficient mice. Blood 97:1990–1998

    Article  CAS  PubMed  Google Scholar 

  • Klinghoffer RA, Mueting-Nelsen PF, Faerman A, Shani M, Soriano P (2001) The two PDGF receptors maintain conserved signaling in vivo despite divergent embryological functions. Mol Cell 7:343–354

    CAS  PubMed  Google Scholar 

  • Krause D, Kunz J, Dermietzel R (1992) Cerebral pericytes—a second line of defence in controlling blood-brain barrier peptide metabolism. In: Drewes LR, Betz AL (eds) Frontiers in cerebral vascular biology: transport and its regulation. Raven, New York

  • Kuo CT, Veselits ML, Barton KP, Lu MM, Clendenin C, Leiden JM (1997) The LKLF transcription factor is required for normal tunica media formation and blood vessel stabilization during murine embryogenesis. Genes Dev 11:2996–3006

    CAS  PubMed  Google Scholar 

  • Larsson J, Goumans M-J, Jansson Sjöstrand L, van Rooijen MA, Ward D, Leveen P, Xu X, ten Dijke P, Mummery CL, Karlsson S (2001) Abnormal angiogenesis but intact hematopoietic potential in TGF-β type I receptor deficient mice. EMBO J 20:1663–1673

    Article  CAS  PubMed  Google Scholar 

  • Levéen P, Pekny M, Gebre-Medhin S, Swolin B, Larsson E, Betsholtz C (1994) Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities. Genes Dev 8:1875–1887

    CAS  PubMed  Google Scholar 

  • Li DY, Sorensen LK, Brooke BS, Urness LD, Davis EC, Taylor DG, Boak BB, Wendel DP (1999) Defective angiogenesis in mice lacking endoglin. Science 284:1534–1537

    Article  CAS  PubMed  Google Scholar 

  • Lindahl P, Johansson BR, Levéen P, Betsholtz C (1997) Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277:242–245

    Article  CAS  PubMed  Google Scholar 

  • Lindahl P, Hellstrom M, Kalen M, Karlsson L, Pekny M, Pekna M, Soriano P, Betsholtz C (1998) Paracrine PDGF-B/PDGF-R beta signaling controls mesangial cell development in kidney glomeruli. Development 125:3313–3322

    CAS  PubMed  Google Scholar 

  • Liu Y, Wada R, Yamashita T, Mi Y, Deng CX, Hobson JP, Rosenfeldt HM, Nava VE, Chae SS, Lee MJ, et al. (2000) Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. J Clin Invest 106:951–961

    CAS  PubMed  Google Scholar 

  • Matsusaka T (1970) Ultrastructural differences between the choriocapillaries and retinal capillaries on the human eye. Jpn J Ophthalmol 14:58–71

    Google Scholar 

  • Nehls V, Drenckhahn D (1991) Heterogeneity of microvascular pericytes for smooth muscle type alpha-actin. J Cell Biol 113:147–154

    CAS  PubMed  Google Scholar 

  • Nehls V, Dreckhahn D (1993) The versatility of microvascular pericytes: from mesenchyme to smooth muscle? Histochemistry 99:1–12

    Google Scholar 

  • Nehls V, Denzer K, Drenckhahn D (1992) Pericyte involvement in capillary sprouting during angiogenesis in situ. Cell Tissue Res 270:469–474

    CAS  PubMed  Google Scholar 

  • Oh SP, Seki T, Goss KA, Imamura T, Yi Y, Donahoe PK, Li L, Miyazono K, ten Dijke P, Kim S, Li E (2000) Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis. Proc Natl Acad Sci U S A 97:2626–2631

    Article  CAS  PubMed  Google Scholar 

  • Ohlsson R, Falck P, Hellstrom M, Lindahl P, Bostrom H, Franklin G, Ahrlund-Richter L, Pollard J, Soriano P, Betsholtz C (1999) PDGFB regulates the development of the labyrinthine layer of the mouse fetal placenta. Dev Biol 212:124–136

    Article  CAS  PubMed  Google Scholar 

  • Orlidge A, D'Amore PA (1987) Inhibition of capillary endothelial cell growth by pericytes and smooth muscle cells. J Cell Biol 105:1455–1462

    CAS  PubMed  Google Scholar 

  • Oshima M, Oshima H, Taketo MM (1996) TGF-β receptor type II deficiency results in defects of yolk sac hematopoiesis and vasculogenesis. Dev Biol 179:297–302

    Google Scholar 

  • Ozerdem U, Grako KA, Dahlin-Huppe K, Monosov E, Stallcup WB (2001) NG2 proteoglycan is expressed exclusively by mural cells during vascular morphogenesis. Dev Dyn 222:218–227

    Article  CAS  PubMed  Google Scholar 

  • Patan S (1998) TIE1 and TIE2 receptor tyrosine kinases inversely regulate embryonic angiogenesis by the mechanism of intussusceptive microvascular growth. Microvasc Res 56:1–21

    Article  CAS  PubMed  Google Scholar 

  • Reynolds LP, Grazul-Bilska AT, Redmer DA (2000) Angiogenesis in the corpus luteum. Endocrine 12:1–9

    CAS  PubMed  Google Scholar 

  • Richardson TP, Peters MC, Ennett AB, Mooney DJ (2001) Polymeric system for dual growth factor delivery. Nat Biotechnol 19:1029–1034

    Article  CAS  PubMed  Google Scholar 

  • Risau W, Flamme I (1995) Vasculogenesis. Annu Rev Cell Dev Biol 11:73–91

    Google Scholar 

  • Ruiter DJ, Schlingemann RO, Westphal JR, Denijn M, Rietveld FJ, De Waal RM (1993) Angiogenesis in wound healing and tumor metastasis. Behring Inst Mitt 92:258–272

    CAS  PubMed  Google Scholar 

  • Sakagami KK, Odama T, Puro DG (2001) PDGF-induced coupling of function with metabolism in microvascular pericytes in the retina. Invest Ophthalmol Vis Sci 42:1939–1944

    CAS  PubMed  Google Scholar 

  • Sato Y, Rifkin DB (1989) Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor beta 1-like molecule by plasmin during co-culture. J Cell Biol 109:309–315

    CAS  PubMed  Google Scholar 

  • Sato Y, Tsuboi R, Lyons R, Moses H, Rifkin DB (1990) Characterization of the activation of latent TGF-beta by co-cultures of endothelial cells and pericytes or smooth muscle cells: a self-regulating system. J Cell Biol 111:757–763

    CAS  PubMed  Google Scholar 

  • Shaheen R, Tseng WW, Davis DW, Liu W, Reinmuth N, Vellagas R, Wieczorek AA, Ogura Y, McConkey DJ, Drazan KE, et al. (2001) Tyrosine kinase inhibitors of multiple angiogenic growth factor receptors improves survival in mice bearing colon cancer liver metastases by inhibition of endothelial cell survival mechanisms. Cancer Res 61:1464–1468

    CAS  PubMed  Google Scholar 

  • Sims DE (1986) The pericyte—a review. Tissue Cell 18:153–174

    CAS  PubMed  Google Scholar 

  • Sims DE (1991) Recent advances in pericyte biology—implications for health and disease. Can J Cardiol 7:431–443

    CAS  PubMed  Google Scholar 

  • Sims DE (2000) Diversity within pericytes. Clin Exp Pharmacol Physiol 27:842–846

    Article  CAS  PubMed  Google Scholar 

  • Sims DE, Westfall JA (1983) Analysis of relationships between pericytes and gas exchange capillaries in neonatal and mature bovine lungs. Microvasc Res 25:333–342

    CAS  PubMed  Google Scholar 

  • Soriano P (1994) Abnormal kidney development and hematological disorders in PDGF beta-receptor mutant mice. Genes Dev 8:1888–1896

    CAS  PubMed  Google Scholar 

  • Stalmans I, Yin-Shan N, Rohan R, Fruttiger M, Bouché A, Ÿuce A, Fijusawa H, Hermans B, Shani M, Jansen S, et al. (2002) Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms. J Clin Invest 109:327–336

    Article  CAS  PubMed  Google Scholar 

  • Sundberg C, Ivarsson M, Gerdin B, Rubin K (1996) Pericytes as collagen producing cells in excessive dermal scarring. Lab Invest 74:452–466

    CAS  PubMed  Google Scholar 

  • Sundberg C, Kowanetz M, Brown LF, Detmar M, Dvorak HF (2002) Stable expression of angiopoietin-1 and other markers by cultured pericytes: phenotypic similarities to a subpopulation of cells in maturing vessels during later stages of angiogenesis in vivo. Lab Invest 82:387–401

    CAS  PubMed  Google Scholar 

  • Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopolous GD (1996) Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic development. Cell 87:1171–1180

    CAS  PubMed  Google Scholar 

  • Tallquist MD, Klinghoffer RA, Heuchel R, Meuting-Nelsen PF, Corrin PD, Heldin C-H, Johnson RJ, Soriano P (2000) Retention of PDGFR-beta function in mice in the absence of phosphatidylinositol 3'-kinase and phospholipase C signaling pathways. Genes Dev 14:3179–3190

    Article  CAS  PubMed  Google Scholar 

  • Tidhar A, Reichenstein M, Cohen D, Faerman A, Copeland NG, Gilbert DJ, Jenkins NA, Shani M (2001) A novel transgenic marker for migrating limb muscle precursors and for vascular smooth muscle cells. Dev Dyn 220:60–73

    Article  CAS  PubMed  Google Scholar 

  • Tilton RG, Kilo C, Williamson JR (1979) Pericyte-endothelial relationships in cardiac and skeletal muscle capillaries. Microvasc Res 18:325–335

    CAS  PubMed  Google Scholar 

  • Uemura A, Ogawa M, Hirashima M, Fujiwara T, Koyama S, Takagi H, Honda Y, Wiegand SJ, Yancopoulos GD, Nishikawa S (2002) Recombinant angiopoietin-1 restores higher-order architecture of growing blood vessels in mice in the absence of mural cells. J Clin Invest 110:1619–1628

    Article  CAS  PubMed  Google Scholar 

  • van Heyningen P, Calver AR, Richardson WR (2001) Control of progenitor cell number by mitogen supply and demand. Curr Biol 11:232–241

    Article  PubMed  Google Scholar 

  • Vikkula M, Boon LM, Carraway KL III, Calvert JT, Diamonti AJ, Goumnerov B, Pasyk KA, Marchuk DA, Warman ML, Cantley LC, et al. (1996) Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2. Cell 87:1181–1190

    CAS  PubMed  Google Scholar 

  • Vrancken Peeters MP, Gittenberger-de Groot AC, Mentink MM, Poelmann RE (1999) Smooth muscle cells and fibroblasts of the coronary arteries derive from the epithelial-mesenchymal transformation of the epicardium. Anat Embryol (Berl) 199:367–378

    Google Scholar 

  • Yamashita J, Itoh H, Hirashima M, Ogawa M, Nishikawa S, Yurugi T, Naito M, Nakao K, Nishikawa S (2000) Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature 408:92–96

    Article  CAS  PubMed  Google Scholar 

  • Yang X, Castilla LH, Xu X, Li C, Gotay J, Weinstein M, Liu PP, Deng CX (1999) Angiogenesis defects and mesenchymal apoptosis in mice lacking SMAD5. Development 126:1571–1580

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements.

The authors thank Mats Hellström and Alexandra Abramsson for providing tissue specimens for Fig. 1a,b.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christer Betsholtz.

Additional information

The images were captured using a Leica confocal microscope, the purchase of which was made possible though a generous grant from the IngaBritt and Arne Lundberg's Research Foundation

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gerhardt, H., Betsholtz, C. Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res 314, 15–23 (2003). https://doi.org/10.1007/s00441-003-0745-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-003-0745-x

Keywords

Navigation