In Vitro Study of Human Immune Responses to Hyaluronic Acid Hydrogels, Recombinant Spidroins and Human Neural Progenitor Cells of Relevance to Spinal Cord Injury Repair
Chenhong Lin,
Åsa Ekblad-Nordberg,
Jakob Michaëlsson,
Cecilia Götherström,
Chia-Chen Hsu,
Hua Ye,
Jan Johansson,
Anna Rising,
Erik Sundström,
Elisabet Åkesson
Affiliations
Chenhong Lin
Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, SE-171 64 Stockholm, Sweden
Åsa Ekblad-Nordberg
Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, SE-141 52 Stockholm, Sweden
Jakob Michaëlsson
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, SE-141 86 Stockholm, Sweden
Cecilia Götherström
Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, SE-141 52 Stockholm, Sweden
Chia-Chen Hsu
Department of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Oxford OX3 7DQ, UK
Hua Ye
Department of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Oxford OX3 7DQ, UK
Jan Johansson
Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 83 Stockholm, Sweden
Anna Rising
Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 83 Stockholm, Sweden
Erik Sundström
Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, SE-171 64 Stockholm, Sweden
Elisabet Åkesson
Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, SE-171 64 Stockholm, Sweden
Scaffolds of recombinant spider silk protein (spidroin) and hyaluronic acid (HA) hydrogel hold promise in combination with cell therapy for spinal cord injury. However, little is known concerning the human immune response to these biomaterials and grafted human neural stem/progenitor cells (hNPCs). Here, we analyzed short- and long-term in vitro activation of immune cells in human peripheral blood mononuclear cells (hPBMCs) cultured with/without recombinant spidroins, HA hydrogels, and/or allogeneic hNPCs to assess potential host–donor interactions. Viability, proliferation and phenotype of hPBMCs were analyzed using NucleoCounter and flow cytometry. hPBMC viability was confirmed after exposure to the different biomaterials. Short-term (15 h) co-cultures of hPBMCs with spidroins, but not with HA hydrogel, resulted in a significant increase in the proportion of activated CD69+ CD4+ T cells, CD8+ T cells, B cells and NK cells, which likely was caused by residual endotoxins from the Escherichia coli expression system. The observed spidroin-induced hPBMC activation was not altered by hNPCs. It is resource-effective to evaluate human compatibility of novel biomaterials early in development of the production process to, when necessary, make alterations to minimize rejection risk. Here, we present a method to evaluate biomaterials and hPBMC compatibility in conjunction with allogeneic human cells.
