Abstract
Platelet-rich plasma (PRP) is a plasma fraction in which several growth factors are concentrated at high levels. In recent years, the biological effects on various cells of the active soluble releasate that is isolated following platelet activation of PRP [PRP-releasate (PRPr)] have been reported. The purpose of this study was to determine the angiogenic effects of human PRPr in vitro and in vivo. PRPr was prepared from human whole blood using the double spin method and was activated with CaCl2 and autologous thrombin. PRPr stimulated proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) and in vivo angiogenesis-inducing ability in nude mice. PRPr led to the phosphorylation of Erk1/2 and Akt in HUVECs, and the induction of proliferation and migration by PRPr was suppressed by PRPr inhibitors PD98059 and LY294002. PRPr induces angiogenesis in vitro and in vivo, and the present findings suggest that the mechanism for this is activation of the ERK and phosphatidylinositol-3-kinase–Akt pathways. Our results demonstrate that PRPr is a promising autologous source for therapeutic angiogenesis in treating cardiovascular disease.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Marx RE (2004) Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg 62:489–496
Margolis DJ, Kantor J, Santanna J, Strom BL, Berlin JA (2001) Effectiveness of platelet releasate for the treatment of diabetic neuropathic foot ulcers. Diabetes Care 24:483–488
Li WW, Talcott KE, Zhai AW, Kruger EA, Li V (2005) The role of therapeutic angiogenesis in tissue repair and regeneration. Adv Skin Wound Care 18:491–500
Anitua E, Andia I, Ardanza B, Nurden P, Nurden AT (2004) Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost 91:4–15
Kakudo N, Minakata T, Mitsui T, Kushida S, Notodihardjo FZ, Kusumoto K (2008) Proliferation-promoting effect of platelet-rich plasma on human adipose-derived stem cells and human dermal fibroblasts. Plast Reconstr Surg 122:1352–1360
Boyapati L, Wang HL (2006) The role of platelet-rich plasma in sinus augmentation: a critical review. Implant Dent 15:160–170
Liu Y, Kalen A, Risto O, Wahlstrom O (2002) Fibroblast proliferation due to exposure to a platelet concentrate in vitro is pH dependent. Wound Repair Regen 10:336–340
Lucarelli E, Beccheroni A, Donati D (2003) Platelet-derived growth factors enhance proliferation of human stromal stem cells. Biomaterials 24:3095–3100
Kanno T, Takahashi T, Tsujisawa T, Ariyoshi W, Nishihara T (2005) Platelet-rich plasma enhances human osteoblast-like cell proliferation and differentiation. J Oral Maxillofac Surg 63:362–369
Favot L, Keravis T, Holl V, Le Bec A, Lugnier C (2003) VEGF-induced HUVEC migration and proliferation are decreased by PDE2 and PDE4 inhibitors. Thromb Haemost 90:334–343
Masamune A, Kikuta K, Watanabe T, Satoh K, Hirota M, Shimosegawa T (2008) Hypoxia stimulates pancreatic stellate cells to induce fibrosis and angiogenesis in pancreatic cancer. Am J Physiol Gastrointest Liver Physiol 295:709–717
Kushida S, Kakudo N, Suzuki K, Kusumoto K (2013) Effects of platelet-rich plasma on proliferation and myofibroblastic differentiation in human dermal fibroblasts. Ann Plast Surg (in press)
Kilian O, Flesch I, Wenisch S (2004) Effects of platelet growth factors on human mesenchymal stem cells and human endothelial cells in vitro. Eur J Med Res 9:337–344
Frechette JP, Martineau I, Gagnon G (2005) Platelet-rich plasmas: growth factor content and roles in wound healing. J Dent Res 84:434–439
Park HB, Yang JH, Chung KH (2011) Characterization of the cytokine profile of platelet rich plasma (PRP) and PRP-induced cell proliferation and migration: upregulation of matrix metalloproteinase-1 and -9 in HaCaT cells. Korean J Hematol 46:265–273
Folkman J, D’Amore PA (1996) Blood vessel formation: what is its molecular basis? Cell 87:1153–1155
Risau W (1997) Mechanisms of angiogenesis. Nature 386:671–674
Folkman J (1986) How is blood vessel growth regulated in normal and neoplastic tissue? G.H.A. Clowes memorial Award lecture. Cancer Res 46:467–473
Li ZJ, Choi HI, Choi DK (2012) Autologous platelet-rich plasma: a potential therapeutic tool for promoting hair growth. Dermatol Surg 38:1040–1046
Gruber R, Karreth F, Kandler B (2004) Platelet-released supernatants increase migration and proliferation, and decrease osteogenic differentiation of bone marrow-derived mesenchymal progenitor cells under in vitro conditions. Platelets 15:29–35
Kakudo N, Kushida S, Minakata T, Suzuki K, Kusumoto K (2011) Platelet-rich plasma promotes epithelialization and angiogenesis in a split thickness skin graft donor site. Med Mol Morphol 44:233–236
Bir SC, Esaki J, Marui A (2011) Therapeutic treatment with sustained-release platelet-rich plasma restores blood perfusion by augmenting ischemia-induced angiogenesis and arteriogenesis in diabetic mice. J Vasc Res 48:195–205
Kakudo N, Kushida S, Ogura T, Hara T, Suzuki K, Kusumoto K (2012) The use of autologous platelet-rich plasma in the treatment of intractable skin ulcer: a case series. OJRM 1:29–32
Acknowledgments
We are grateful to Prof. S. Taketani (Department of Biotechnology, Kyoto Institute of Technology) for his helpful comments.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kakudo, N., Morimoto, N., Kushida, S. et al. Platelet-rich plasma releasate promotes angiogenesis in vitro and in vivo. Med Mol Morphol 47, 83–89 (2014). https://doi.org/10.1007/s00795-013-0045-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00795-013-0045-9