Table 1.

In vitro studies on L-PRP for tendon models.

Study (author, Year)	System used to Obtain L-PRP/cytologic findings	Type of cells	Study design	Time of analysis	Outcomes measured	Results (L-PRP compared with control)
Zhang et al. [28]	Leukocytes in L-PRP were 4 times higher than whole blood; leukocytes in P-PRP were 2 times lower than whole blood	TSCs	L-PRP was prepared from rabbits. TSCs were isolated from the patellar tendons of healthy rabbits. TSCs cultured and treated with DMEM with FBS (control group), P-PRP, or L-PRP	1 week	Cell proliferation, collagen production, apoptosis, expression of specific growth factors, nontenocyte-related genes, and inflammation-related genes	Cell proliferation↓, collagen production↑, apoptosis↑, expression of specific growth factors (VEGF, EGF, TGF-β1, and PDGF)↑, nontenocyte-related genes (PPAR, SOX-9, and Runx-2)↑, inflammation-related genes (IL-1β and mPGES)↑
Yu et al. [27]	5.404 ± 0.646 × 103/ml (WBC in whole blood 6.568 ± 1.029 × 103/ml (WBC in L-PRP)	Tendon cell	L-PRP was prepared from rats. Tendon cells were obtained from rats, were cultured, and sampled from normal fibroblast shape. Cells were then cultured in serum-free medium under five different conditions: Medium only (control), or 0.1%, 0.5%, 1% or 2% L-PRP	24 h	Cell proliferation, expression of specific growth factor	Cell proliferation↑in a dose-dependent manner, expression of specific growth factors (TGF-β1 and PDGF) ↑
Schnabel et al. [26]	SmartPReP2 system (Harvest Technologies, Plymouth, MA)	Tendon explants	L-PRP was prepared from young adult horses. Tendon explants from horse normal forelimb flexor digitorum superficialis tendon cultured and treated with whole blood, 10% plasma (as control), L-PRP, PPP, or bone marrow aspirate (BMA) at concentrations of 100%, 50%, or 10%	3 days	Expression of specific growth factor, gene expression of the matrix molecules and catabolic molecules	Expression of specific growth factor (TGF-β1 and PDGF-BB)↑, gene expression of the matrix molecules (COL1, COL3 and COMP) ↑, no increase in catabolic molecules (MMP-3 and MMP-13)
Zhou et al. [29]	5.404 ± 0.646 × 103/ml (WBC in whole blood); 6.568 ± 1.029 × 103/ml (WBC in L-PRP)	TSCs	L-PRP and P-PRP were prepared from rabbits. TSCs were isolated from the patellar tendons of rabbits. TSCs were cultured and treated with control (DMEM + 2%FBS), L-PRP, or P-PRP	2 weeks	Cell proliferation, differentiation of TSCs into active tenocytes, catabolic marker genes, inflammatory genes, tenocyte-related proteins.	Cell proliferation↑in a dose-dependent manner, differentiation of TSCs into active tenocytes↑, catabolic marker genes (MMP-1, MMP-13)↑, inflammatory genes (IL-1β, IL-6, TNF-α)) ↑, tenocyte-related proteins (COL1 and COL3)↑
Rubio-Azpeitia et al. [25]	L-PRP is called by authors 4.7 ± 3.8 × 103/μL (leukocytes in L-PRP).	Tendinopathic cells	L-PRP, PPP, and P-PRP were prepared from 4 healthy donors (2 men and 2 women). Tendon cells were isolated from chronic tendinopathy tissue which comes from supraspinatus tendon biopsy samples obtained from patients undergoing arthroscopic shoulder surgery and cultured and treated with PPP (as control), P-PRP, or L-PRP	96 hours	Cell migration, cell proliferation, expression of genes associated with matrix turnover, inflammatory proteins	Cell migration↑, cell proliferation↑, expression of genes associated with matrix turnover (COL1 and COL3↓, MMP-1 expression↑, Decorin, fibronectin, and aggrecan↓), inflammatory proteins (IL-6↑)
Cross et al. [22]	L-PRP: Biomet GPS III Mini platelet concentrate kit; P-PRP: Arthrex autologous conditioned plasma double Syringe system	Tendon explants	Venous blood was collected from a healthy human volunteer population. Tendon explants were taken from the lateral aspect of patients' chronically torn supraspinatus tendons. Tendons were separated into group 1 (moderate tendinopathy) and group 2 (severe tendinopathy) according to prepared and scored tendon samples histologically. Tendons were cultured and treated with P-PRP, L-PRP, or control media (DMEM with FBS)	96 hours	Matrix gene expression, catabolic gene expression	Matrix gene expression (COL1: COL3 ratio) ↑ (group 1), catabolic gene expression (MMP-9↑ (group 2), IL-1β (group 2))
McCarrel et al. [24]	(5 to10) × 103 (WBC in standard PRP, made by SmartPReP2 system); (25 to 30) × 103 (WBC in L-PRP); (0 to 2) × 103 (WBC in P-PRP)	Tendon explants	PRP was prepared from young adult horses. Tendon explants from horse normal forelimb flexor digitorum superficialis tendon cultured and treated with standard PRP, L-PRP, P-PRP or control (10% plasma in DMEM)	72 h	Growth factor, matrix gene expression, catabolic gene expression	Growth factor (PDGF↑), matrix gene expression (COL1: COL3 ratio↑, COMP↑), catabolic gene expression (MMP-13↓, IL-1β↑, TNF-α↑)
Lin et al. [23]	L-PRP is called by authors; 4.7 ± 3.8 × 103/μL (leukocytes in L-PRP)	Tenocytes	PRP was collected from 3 patients during rotator cuff repair. Tenocytes were isolated from torn human supraspinatus tendons during arthroscopic rotator cuff repair of 3 patients with moderate degenerative rotator cuff tears and were cultured and treated with control (only culture medium supplementation), P-PRP, or L-PRP	3 days	Gene analysis, tenocyte proliferation	Gene analysis (TNC, COL1, COL3, and SCX) ↑, tenocyte proliferation↑

↑, significant increase; ↓, significant decrease; n. a., not affected; TSCs, tendon stem cells; L-PRP, leukocyte- and platelet-rich plasma; P-PRP, pure platelet-rich plasma; PPP, platelet poor plasma; DMEM, Dulbecco's modified Eagle's medium; FBS, fetal bovine serum; VEGF, vascular endothelial growth factor; EGF, epidermal growth factor; TGF-β1, transforming growth factor–β1; PDGF, platelet-derived growth factor; PPAR, peroxisome proliferator-activated receptor; SOX-9, SRY (sex determining region Y)–box 9; Runx-2, runt-related transcription factor 2; IL-1β/6, Interleukin-1β/6; COMP, cartilage oligomeric matrix protein; mPGES, membrane-associated prostaglandin synthase; WBC, white blood cell; COL1, type I collagen; COL3, type III collagen; MMP, matrix metalloproteinase; TNF-α, tumor necrosis factor-α; TNC, tenascin-C; SCX, scleraxis.