Platelet-rich plasma: combinational treatment modalities for musculoskeletal conditions
Isabel Andia1(), Michele Abate2
1. Regenerative Medicine Laboratory, BioCruces Health Research Institute, Cruces University Hospital, 48903 Barakaldo, Spain 2. Department of Medicine and Science of Aging, University G. d’Annunzio, Chieti-Pescara, 66013 Chieti Scalo, Italy
Current research on common musculoskeletal problems, including osteoarticular conditions, tendinopathies, and muscle injuries, focuses on regenerative translational medicine. Platelet-rich plasma therapies have emerged as a potential approach to enhance tissue repair and regeneration. Platelet-rich plasma application aims to provide supraphysiological concentrations of platelets and optionally leukocytes at injured/pathological tissues mimicking the initial stages of healing. However, the efficacy of platelet-rich plasma is controversial in chronic diseases because patients’ outcomes show partial improvements. Platelet-rich plasma can be customized to specific conditions by selecting the most appropriate formulation and timing for application or by combining platelet-rich plasma with synergistic or complementary treatments. To achieve this goal, researchers should identify and enhance the main mechanisms of healing. In this review, the interactions between platelet-rich plasma and healing mechanisms were addressed and research opportunities for customized treatment modalities were outlined. The development of combinational platelet-rich plasma treatments that can be used safely and effectively to manipulate healing mechanisms would be valuable and would provide insights into the processes involved in physiological healing and pathological failure.
L-PRP and PRP enhanced migration and proliferation compared to PPP. PPP and PRP more anabolic than L-PRP. CTGF secretion reduced in L-PRP. L-PRP and PRP more proinflammatory than PPP
Zhang (2016) [52]
L-PRP versus PRP
Rabbit tendon stem cells
Proliferation ↓; apoptosis ↑; TSC in L-PRP differentiated into non-tenocytes; mPGEs ↑; IL-1β ↑
Zhou (2015) [53]
L-PRP versus PRP
Rabbit tendon stem cells
Gene and protein expression: MM-1↑; MMP-13↑; IL-1β↑ ; IL6↑ ; TNFα↑. PGE2↑. Col1↓; col3↓; α-SMA↓
p-PRP stimulated aggrecan and Col2; L-PRP induced HAS2 and promoted catabolic activation
Freymann (2016) [59]
ACP, PRP and human serum
Human meniscus cells
Serum enhanced Col1, Col2 and proteoglycan deposition; ACP enhanced aggrecan, COMP and biglycan expression
Jalowiec (2016) [60]
Platelet concentration/µL in the gel: 106; 2×106; 10×106
Human mesenchymal stem cells
Highest cell viability in PRP gels containing 106 platelets/µL
Kreuz (2015) [61]
ACP, Regen, DrPRP (Double Spin) and PRP obtained by apheresis and by centrifugation
Human subchondral mesenchymal precursor cells
Different potential to stimulate chondrogenic differentiation, migration and proliferation. ACP, Regen and DrPRP produced fibrous tissue in contrast to the other PRPs
Osterman (2015) [62]
L-PRP and PRP versus controls
Human coculture cartilage and synovium (OA patients) IL-1β pretreated
ACAN ↑; ADAMTS-5 ↓ (cartilage and synovium), Col1; VEGF; TIMP-1 ↓(cartilage and synovium) No differences in the anti-inflammatory effects between the 2 formulations (nitric oxide production)
Pifer (2014) [39]
High L-PRP versus low pure PRP
Human ligament fibroblast IL-1β pretreatment 24h/48h
MMP2 ↓; MMP3 ↓, MMP9 ↑
Rios (2015) [63]
L-PRP versus PRP
Horse cartilage explants pre-treated with LPS
PDGF-BB↑; TGF-β1↑; TNF-α↑; IL-4 ↑;IL-1ra↑
Muscle injuries [30,68]
Denapoli (2016) [30]
High L-PRP low pure PRP and PPP
Rat muscle in vitro and in vivo
EGF ↑; HGF ↑; IGF ↑; PDGF-AA, -BB both ↑; TGF-β1 ↑; VEGF ↑(only in L-PRP); sFlt-1 ↓
Mazzocca (2012) [68]
Pure PRP (low and high platelets) L-PRP versus 2% and 10% FBS
In vitro, human muscle, bone and tendon cells
Cell proliferation: low platelet PRP increased proliferation of myocytes and tenocytes but not clear evidences favoring any of the tested formulations
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