Platelet-rich plasma releasate promotes differentiation of tendon stem cells into active tenocytes.
BACKGROUND
Platelet-rich plasma (PRP) has been used to enhance tendon healing in clinical settings. However, the cellular mechanisms underlying PRP treatment of injured tendons remain unclear. The aim of this study was to determine the effects of PRP, in the form of PRP-clot releasate (PRCR), on tendon stem cells (TSCs), a newly discovered cell population in tendons.


OBJECTIVE
The PRCR treatment promotes differentiation of TSCs into tenocytes that are activated to proliferate quickly and increase collagen production.


METHODS
Controlled laboratory study.


METHODS
After PRCR treatment, cell morphology, expression of stem/progenitor cell marker nucleostemin, and population doubling time were examined. In addition, gene and protein analyses were performed using reverse transcription-polymerase chain reaction, immunocytochemistry, and Western blot to characterize the type of cells that had differentiated after PRCR treatment.


RESULTS
The TSCs without PRCR treatment were small and exhibited an irregular shape, whereas with increasing PRCR dosage, TSCs became large, well spread, and highly elongated with downregulation of nucleostemin expression. The PRCR treatment also markedly enhanced TSC proliferation, tenocyte-related gene and protein expression, and total collagen production, all of which indicated that PRCR treatment induced differentiation of TSCs into activated tenocytes.


CONCLUSIONS
The PRCR treatment promotes differentiation of TSCs into active tenocytes exhibiting high proliferation rates and collagen production capability.


CONCLUSIONS
The findings of this study suggest that PRP treatment of injured tendons is "safe" as it promotes TSC differentiation into tenocytes rather than nontenocytes, which would compromise the structure and function of healing tendons by formation of nontendinous tissues. Moreover, they suggest that PRP treatment can enhance tendon healing because tenocytes induced to differentiate by PRP are activated to proliferate quickly and produce abundant collagen to repair injured tendons that have lost cells and matrix.
Zhang
Jianying
J
Department of Orthopaedic Surgery, University of Pittsburgh, PA 15213, USA.
Wang
James H-C
JH
D000704:Analysis of Variance; D000818:Animals; D001792:Blood Platelets; D015153:Blotting, Western; D003094:Collagen / Q000096:biosynthesis; D004195:Disease Models, Animal; D019204:GTP-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013708:Tendon Injuries / Q000473:pathology / Q000628:therapy*; D013710:Tendons / Q000166:cytology* / Q000201:enzymology / Q000473:pathology
C469949:GNL3 protein, human; D009687:Nuclear Proteins; D003094:Collagen; D019204:GTP-Binding Proteins