Platelet-rich plasma: combinational treatment modalities for musculoskeletal conditions

doi:10.1007/s11684-017-0551-6

Front. Med.

2018, Vol. 12

Issue (2) : 139-152 https://doi.org/10.1007/s11684-017-0551-6

REVIEW

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

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Abstract

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.

Keywords regenerative medicine joint conditions muscle injuries platelet rich plasma tendinopathy healing mechanisms

Corresponding Author(s): Isabel Andia

Just Accepted Date: 08 August 2017 Online First Date: 31 October 2017 Issue Date: 02 April 2018

Cite this article:

Isabel Andia,Michele Abate. Platelet-rich plasma: combinational treatment modalities for musculoskeletal conditions[J]. Front. Med., 2018, 12(2): 139-152.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-017-0551-6
https://academic.hep.com.cn/fmd/EN/Y2018/V12/I2/139

Fig.1 PRP secretome triggers several compartments. (A) Infiltrating immune compartment, which includes neutrophils, monocytes/macrophages, and T cells. PRP also influences macrophage polarization and pro-inflammatory (M1) versus pro-resolving (M2). (B) Several molecules contained in PRP modulate angiogenesis by influencing endothelial cell migration, proliferation, and cell sprouting. (C) PRP also influences the activities of resident cells located in the stromal compartment. PRP can stimulate tissue regeneration by modulating the crosstalk between infiltrating and local cells.

Author (year)	PRP formulation	Cell phenotype	Biological effects
Tendon conditions [⁴⁷–⁵³]
Boswell (2014) [⁴⁷]	L-PRP and PRP, different ratios platelet:leukocytes (370:1; 1490:1; 4821:1)	Superficial profundus tendons from healthy horses	Col1 ↑; Col3 ↓, COMP ↑, MMP-3=, MMP-13↓, IL-1β = Inverse correlation Col1 and platelet count
Cross (2015) [⁴⁸]	L-PRP versus PRP	Diseased supraspinatus tendon cells Moderately and severely degenerated (human)	Gene expression: Col1; Col3; Col1/col3 ↓ in moderately no differences in severely degenerated; COMP=; MMP-9 ↓ in severely degenerated= in moderately; MMP-13=; IL-1β ↓; TGF-β1 ↑ Protein secretion: IL-1β; IL-1Ra; IL-1β/IL-1Ra ↑in L-PRP; in moderately degenerated; IL-6= in moderately, ↓ in severely degenerated; IL-8= ; MMP-9 ↑; TGF-β1 ↑
Jo (2012) [⁴⁹]	PPP and PRP with different platelet concentrations (1000×10³/µL vs. PPP)	Tenocytes from patients with rotator cuff degenerative tears	Col1 ↑ (Day 7 not Day 14), Col3 ↑(days 7 and 14) Col1/col3=; decorin ↑(day 14), tenascin ↑ (day 7 and 14), scleraxis ↑(day 14), GAGs ↑(day 14)
McCarrel (2012) [⁵⁰]	L-PRP versus PRP	Flexor digitorum explants from adult horses	Gene expression: Col1/Col3=; COMP=; MMP13=; IL-1β ↑; TNF-α ↑
Rubio-Azpeitia (2016) [⁵¹]	High L-PRP low pure PRP and PPP	Human tendon cells (healthy and pathologic)	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↓
Joint conditions [³⁹,⁵⁶–⁶³]
Assirelli (2015) [⁵⁶]	L-PRP, PRP and PPP	Human synoviocytes (OA patients)	Gene expression: IL-1β ↑; IL8 ↑; FGF-2 ↑; HGF↓; TIMP-4↓; HAS-1= ; HAS2= ; HAS3=
Braun (2014) [⁵⁷]	High L-PRP versus low pure PRP	Human synoviocytes (OA)	IL-1β ↑; IL6 ↑; TNF-α ↑
Carvallo (2014) [⁵⁸]	pPRP, L-PRP and PPP	Human chondrocytes	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

Tab.1 Experimental studies comparing different PRP formulations

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