The Potential Use of Allogeneic Platelet-Rich Plasma for Large Bone Defect Treatment: Immunogenicity and Defect Healing Efficacy

Abstract

Autologous platelet-rich plasma (PRP) has been extensively investigated for large bone defect treatment, but its clinical application is harassed by controversial outcome, due to highly variable PRP quality among patients. Alternatively, allogeneic PRP from well-characterized donors cannot only generate more consistent and reliable therapeutic effect but also avoid harvesting large quantities of blood, an additional health burdens to patients. However, the use of allogeneic PRP for bone defect treatment is generally less investigated, especially for its immunogenicity in such application. Here, we meticulously investigated the immunogenicity of allogeneic PRP and evaluated its healing efficacy for critical-sized defect treatment. Allogeneic PRP contained 4.1-fold and 2.7- to 4.9-fold higher amount of platelets and growth factors than whole blood, respectively. The intramuscular injection of allogeneic PRP to rabbits did not trigger severe and chronic immunoresponse, evidenced by little change in muscular tissue microstructure and CD4⁺/CD8⁺ T lymphocyte subpopulation in peripheral blood. The implantation of allogeneic PRP/deproteinized bone matrix (DPB) constructs (PRP+DPB) successfully bridged 1.5-cm segmental radial defects in rabbits, achieving similar healing capacity as autologous MSC/DPB constructs (MSC+DPB), with greater bone formation (1.1-1.5×, p<0.05) and vascularization (1.3-1.6×, p<0.05) than DPB alone, shown by histomorphometric analysis, bone mineral density measurement, and radionuclide bone imaging. Furthermore, the implantation of both allogeneic PRP- and autologous MSC-mediated DPB constructs (PRP + MSC + DPB) resulted in the most robust bone regeneration (1.2-2.1×, p<0.05) and vascularization (1.3-2.0×, p<0.05) than others (PRP+DPB, MSC+DPB, or DPB alone). This study has demonstrated the promising use of allogeneic PRP for bone defect treatment with negligible immunogenicity, great healing efficacy, potentially more consistent quality, and no additional health burden to patients; additionally, the synergetic enhancing effect found between allogeneic PRP and autologous MSCs may shed a light on developing new therapeutic strategies for large bone defect treatment.

The effect of intra-articular allogenic platelet rich plasma in Dunkin-Hartley guinea pig model of knee osteoarthritis

“…Thirdly, we have utilized allogeneic PRP prepared from guinea pig blood. Allogeneic PRP has been shown to be non-immunogenic in local application and ensures uniform quantity and quality of platelets 33 . Thus, inter-and intra-organism variability associated with autologous PRP was eliminated by using single source for PRP (allogenic), which permits a more consistent preparation.…”

Controlled delivery of platelet-derived proteins enhances porcine wound healing

“…This protein cocktail has high potential to stimulate an accelerated healing response since it contains numerous factors known to play different vital roles in the natural healing progression. Autologous PRP avoids the risk of an immune response during treatment, although allogenic PRP has also been used safely in a clinical setting without serious adverse effects as long as the platelets were removed [14]. PRP is currently approved for use in orthopedic applications and is under investigation for several others including wound healing [14–18].…”

“…Autologous PRP avoids the risk of an immune response during treatment, although allogenic PRP has also been used safely in a clinical setting without serious adverse effects as long as the platelets were removed [14]. PRP is currently approved for use in orthopedic applications and is under investigation for several others including wound healing [14–18]. There are many ways to prepare PRP though very few studies have utilized consistent methodology, wound types, or patient demographics, which has led to conflicting data regarding its efficacy.…”

Human platelet lysate supplementation of mesenchymal stromal cell delivery: issues of xenogenicity and species variability

“…Variation in platelet properties as a function of animal species has been previously explored, uncovering both significant similarities and differences in the platelet proteome, depending on the study and species examined (van den Dolder et al , ; Yu et al , ). Although delivery of PRP has demonstrated regenerative efficacy within several species‐matched models, including rat and rabbit, the effect of platelet‐derived factors on potentiating co‐delivered, cell‐based therapeutics has not been thoroughly investigated (Rai et al , ; Zhang et al , ). Even in culture, the impact of exposing rMSCs to rPL‐supplemented medium is largely untested in comparison to the well‐established hMSC–hPL relationship.…”