PRP and MSCs on tenocytes artificial wound healing: an in vitro study comparing fresh and frozen PRP

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Abstract

Evolutionary medicine has proven helpful to understand the origin of human disease, e.g. in identifying causal roles of recent environmental changes impacting on human physiology (environment-phenotype mismatch). In contrast, diseases affecting only a limited number of members of a species often originate from evolutionary trade-offs for usually physiologic adaptations assuring reproductive success in the context of extrinsic threats. For example, the G1 and G2 variants of the APOL1 gene supporting control of Trypanosoma infection come with the trade-off that they promote the progression of kidney disease. In this review we extend the concept of evolutionary nephrology by discussing how the physiologic adaptations (danger responses) to tissue injury create evolutionary trade-offs that drive histopathological changes underlying acute and chronic kidney diseases. The evolution of multicellular organisms positively selected a number of danger response programs for their overwhelming benefits in assuring survival such as clotting, inflammation, epithelial healing and mesenchymal healing, i.e. fibrosis and sclerosis. Upon kidney injury these danger programs often present as pathomechanisms driving persistent nephron loss and renal failure. We explore how classic kidney disease entities involve insufficient or overshooting activation of these danger response programs for which the underlying genetic basis remains largely to be defined. Dissecting the causative and hierarchical relationships between danger programs should help to identify molecular targets to control kidney injury and to improve disease outcomes.Tendon tissue has poor regenerative capacity due to its low vascularization, cell density and extracellular matrix (ECM) production. Therefore, tendon injuries are an increasing clinical problem because of the formation of scar tissue with traditional therapies. Regenerative medicine aims at triggering a healing response through the use of biological treatments such as mesenchymal stromal cells (MSCs) and growth factors (GFs). MSCs show several advantages in tendon clinical setting, while platelet rich plasma (PRP) has gained popularity because of its high GF concentration, although its applications in the tendon clinical setting are still controversial. The aim of the present study was to evaluate a combined treatment of MSCs and PRP in an in vitro microwound model of tendon injuries. In addition, fresh and frozen PRP were compared. Single human tenocytes cultures or co-cultures with bone marrow derived MSCs (BMSCs) were set up with or without human PRP, fresh or frozen. After 24 hours of culture, it was observed that MSCs alone significantly increased tenocyte migration speed, microwound healing rate, fibronectin, collagen I and aggrecan production. These effects were enhanced by the combination with PRP, fresh being more effective than frozen PRP. In addition, the number of MSCs and tenocytes inside the microwound was significantly increased, especially with fresh PRP. In conclusion, the combination of MSCs and PRP, especially the fresh one, increases tenocytes and MSC migration speed, as well as ECM protein production compared to the use of MSCs alone.

Original languageEnglish
Pages (from-to)1323-1334
Number of pages12
JournalHistology and Histopathology
Volume33
Issue number12
DOIs
Publication statusPublished - Dec 2018

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Keywords

  • tenocytes
  • mesenchymal stem cells
  • tendon injury
  • tendon healing
  • platelet rich plasma

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