title: 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.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Allen
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Emily B
authors.initials: EB
authors.lastname: Butts
authors.affiliation: Department of Haematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Ian B
authors.initials: IB
authors.lastname: Copland
authors.affiliation: George W. Woodruff School of Mechanical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Hazel Y
authors.initials: HY
authors.lastname: Stevens
authors.affiliation: George W. Woodruff School of Mechanical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Guldberg
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002457:Cell Extracts / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020100:Hydrogels / Q000494:pharmacology; D016867:Immunocompromised Host; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011923:Rats, Nude; D013045:Species Specificity; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D002457:Cell Extracts; D020100:Hydrogels
keywords: cell-based therapeutics; mesenchymal stromal cells; platelet lysate; preclinical rodent models; species variability; xenogenicity