Platelet-Rich Blood Derivatives for Stem Cell-Based Tissue Engineering and Regeneration

Abstract

Platelet rich blood derivatives have been widely used in different fields of medicine and stem cell based tissue engineering. They represent natural cocktails of autologous growth factor, which could provide an alternative for recombinant protein based approaches. Platelet rich blood derivatives, such as platelet rich plasma, have consistently shown to potentiate stem cell proliferation, migration, and differentiation. Here, we review the spectrum of platelet rich blood derivatives, discuss their current applications in tissue engineering and regenerative medicine, reflect on their effect on stem cells, and highlight current translational challenges.

Keywords: autologous growth factors; blood derivatives; cell proliferation; platelet rich plasma; stem cell differentiation; stem cells.

Figures

Figure 1

Preparation protocols of (A) PRP and (B) PRF. (C) Schematic depiction of leucocyte free platelet rich plasma (P-PRP) and platelet rich fibrin (P-PRF), Leucocytes PRP (L-PRP) and = Leucocyte- and platelet-rich plasma. L-PRF = Leucocyte- and platelet-rich fibrin. Fibrin architecture is thicker and more robust in PRF (black arrows) than PRP (red arrows). (Figure 1A Reprinted from: Dhurat R, Sukesh M. Principles and Methods of Preparation of Platelet-Rich Plasma: A Review and Author’s Perspective. Journal of cutaneous and aesthetic surgery;7:189-97, with permission) [9]. (Figures 1B and 1C Reprinted from: Dohan Ehrenfest DM, Rasmusson L, Albrektsson T. Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRF). Trends in biotechnology 2009;27:158-67,, with permission from Elsevier) [83].

Figure 2

Effects of PRP on stem cell proliferation, differentiation potential and bone healing. (A) Effect of different PRP concentrations on the proliferation of bone-marrow derived MSCs [41]. (B) Three-dimensional micro-CT of a bone defect implanted with hydrogels containing either PBS or PRP [84]. (C) Differentiation media supplemented with PRP, bone marrow and adipose derived MSCs exhibit strong differentiation potential towards osteogenic (Alizarin Red S, calcium deposits) and chondrogenic (Toluidine Blue, glycosaminoglycans), but not adipogenic (Oil Red O, lipid accumulation). (Figure 1A Reprinted from: Amable PR, Teixeira MV, Carias RB, et al. Mesenchymal stromal cell proliferation, gene expression and protein production in human platelet-rich plasma-supplemented media. PloS one 2014;9:e104662) [41]. (Figures 1B and 1C Reprinted from: Kim YH, Furuya H, Tabata Y. Enhancement of bone regeneration by dual release of a macrophage recruitment agent and platelet-rich plasma from gelatin hydrogels. Biomaterials 2014;35:214-24, with permission from Elsevier) [84].

Figure 3

Angiogenic effect of PRP on human dermal microvascular endothelial cells. (A) in vitro tube formation assay and (B) mean tube length showing PRP’s proangiogenic effects. (Reprinted from: Mammoto T, Jiang A, Jiang E, et al. Platelet rich plasma extract promotes angiogenesis through the angiopoietin1-Tie2 pathway. Microvascular research 2013;89:15-24, with permission from Elsevier) [60].

Figure 4

Arthroscopic intra-articular view of an osteoarthritic knee (A) before treatment demonstrating cartilage defects on the articular surface and (B) 17 months post treatment with MSC and PRP, which demonstrates significant cartilage regeneration on defect site. (Reprinted from: Koh Y-G, Kwon O-R, Kim Y-S, et al. Comparative outcomes of open-wedge high tibial osteotomy with platelet-rich plasma alone or in combination with mesenchymal stem cell treatment: a prospective study. Arthroscopy: the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association 2014;30:1453-60, with permission from Elsevier) [78].

Figure 5

Application of MSCs, PRP and hyaluronic acid in papilla regeneration in patients with Black Triangle defect. (A) Schematic depiction of the preparation and injection procedure. (B) Photographs that visualize the defect’s healing during i) pretreatment, ii) treatment, iii) 3, iv) 6, v) 12, and vi) 36 months post treatment. (Reprinted from: Yamada Y, Nakamura S, Ueda M, et al. Papilla regeneration by injectable stem cell therapy with regenerative medicine: long-term clinical prognosis. Journal of Tissue Engineering and Regenerative Medicine 2015;9:305-9, with permission from Wiley) [80].