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

Abstract

Immunogenicity of fetal bovine serum (FBS) poses a problem for its use in the propagation of autologous mesenchymal stromal cells (MSCs) for cell therapy. Human platelet lysate (hPL), an enriched growth factor solution containing mitogenic and angiogenic cues, has potential utility in replacing FBS for human MSC (hMSC) delivery strategies. Despite its potentiation of hMSC number in vitro, little is known concerning its capacity to supplement implanted hMSC-seeded constructs and promote tissue regeneration in vivo. In this study, we tested the effects of incorporating hPL in cell-seeded constructs implanted subcutaneously into immunocompromised rats, investigated in vitro interactions between hPL and rat MSCs (rMSCs) and determined interspecies variability in the PL product [hPL vs rat PL (rPL)] and its effect on cultured MSCs (hPL/hMSCs vs rPL/rMSCs). The overarching aim was to determine the utility of hPL to foster MSC survival in preclinical rodent models. Exposure to hPL-supplemented media resulted in rMSC death, by a process attributable to heat-labile proteins, but not membrane attack complex formation. In the in vitro syngeneic model, the rodent product proved fundamentally distinct from the human product, with rPL having substantially lower growth factor content than hPL. Moreover, contrary to the positive effects of hPL on hMSC expansion, rPL did not reduce rMSC doubling time for the serum concentrations examined. When tested in vivo, hPL did not improve cell survival within hydrogel constructs through 2 weeks postimplantation. In summary, this study highlights the many facets of xenogenicity and interspecies variability that must be considered in the preclinical evaluation of hPL. Copyright © 2016 John Wiley & Sons, Ltd.

Biomimetic microenvironmental preconditioning enhance neuroprotective properties of human mesenchymal stem cells derived from Wharton's Jelly (WJ-MSCs)

“…It also enhanced endothelial cell sprouting alone and in co-culture with MSCs 41 . However, other research found that human PL did not improve cell survival within hydrogel constructs beyond 2 weeks post-implantation 42 . This finding may be explained as being dose dependent as shown in an experiment with MSCs derived from dental pulp.…”

Inhibition of hypertrophy and improving chondrocyte differentiation by MMP-13 inhibitor small molecule encapsulated in alginate-chondroitin sulfate-platelet lysate hydrogel

“…Platelet lysate is a cocktail of growth factors, anti-inflammatory cytokines, and clot-forming proteins that are involved in tissue repair processes [ 47 , 48 ]. PL is a cost-effective and autologous source of growth factors compared to recombinant growth factors [ 49 ]. Studies suggest that PL significantly increases MSC proliferation compared with fetal bovine serum (FBS) in vitro.…”

“…In addition, PL enhances chondrogenic differentiation of MSCs [ 52 ]. However, there are two main drawbacks for PL as scaffold in tissue engineering: a high degradation rate and low mechanical properties [ 49 , 53 ]. Therefore, the mechanical stability of PL-based hydrogels for long-term applications needs to be improved.…”

Human platelet lysate supports the formation of robust human periodontal ligament cell sheets

“…Moreover, MSCs expanded in PL‐supplemented culture medium exhibited preserved immune‐privileged capacities, such as the suppression of T cell proliferation and activation (Flemming et al, ); such features enabled these cells to be used for treating graft‐vs‐host disease in clinical trials (Introna et al, ). Recently, the utility of human PL to foster cell survival in vivo was also accessed in animal models (Allen, Butts, Copland, Stevens, & Guldberg, ). Although xenogenicity and species variability may affect the preclinical outcome, human‐derived PL has the potential to be applied in important future developments in regenerative medicine.…”