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Cited by 90Tissue Engineering and Regenerative MedicineHydrogels: synthesis, properties, applicationsXenotransplantation and immune response

Humanized mouse model for assessing the human immune response to xenogeneic and allogeneic decellularized biomaterials

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Wang, Raymond M., Johnson, Todd D., He, Jingjin, Rong, Zhili, Wong, Michelle, Nigam, Vishal, Behfar, Atta, Xu, Yang +1 more·2017·Biomaterials
DOI 10.1016/j.biomaterials.2017.03.016PMC PMC5434867
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Abstract

Current assessment of biomaterial biocompatibility is typically implemented in wild type rodent models. Unfortunately, different characteristics of the immune systems in rodents versus humans limit the capability of these models to mimic the human immune response to naturally derived biomaterials. Here we investigated the utility of humanized mice as an improved model for testing naturally derived biomaterials. Two injectable hydrogels derived from decellularized porcine or human cadaveric myocardium were compared. Three days and one week after subcutaneous injection, the hydrogels were analyzed for early and mid-phase immune responses, respectively. Immune cells in the humanized mouse model, particularly T-helper cells, responded distinctly between the xenogeneic and allogeneic biomaterials. The allogeneic extracellular matrix derived hydrogels elicited significantly reduced total, human specific, and CD4+ T-helper cell infiltration in humanized mice compared to xenogeneic extracellular matrix hydrogels, which was not recapitulated in wild type mice. T-helper cells, in response to the allogeneic hydrogel material, were also less polarized towards a pro-remodeling Th2 phenotype compared to xenogeneic extracellular matrix hydrogels in humanized mice. In both models, both biomaterials induced the infiltration of macrophages polarized towards a M2 phenotype and T-helper cells polarized towards a Th2 phenotype. In conclusion, these studies showed the importance of testing naturally derived biomaterials in immune competent animals and the potential of utilizing this humanized mouse model for further studying human immune cell responses to biomaterials in an in vivo environment.

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  • There are contradictory data about the degenerative effects of remaining α-gal epitopes within decellularized tissues.

    “However, there are contradictory data about the degenerative effects of remaining α-gal epitopes within decellularized tissues [53, 122, 123].”

    From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [122]

    The Discussion (page unavailable) acknowledges concern about residual α-gal epitopes in processed xenogeneic materials, but says adverse reactions in human patients have not been shown or proven. It does not describe contradictory data about degenerative effects in decellularized tissues. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

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References 58 · Cited by 90

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Authors
Wang, R. M., Johnson, T. D., He, J., Rong, Z., Wong, M., Nigam, V., Behfar, A., Xu, Y., & Christman, K. L.
Affiliations
  • University of California San Diego (US)
  • Mayo Clinic (US)
Corresponding author
Christman, Karen L.
ORCID
Venue
Biomaterials
Publisher
Elsevier BV
Published
2017-06
Volume
129
Pages
98-110
ISSN
0142-9612 (ISSN-L)
DOI
10.1016/j.biomaterials.2017.03.016
PMC
PMC5434867
OpenAlex
W2592704774
Cited by
90
References
58
Citations by year
2026: 4 · 2025: 6 · 2024: 10 · 2023: 13 · 2022: 12 · 2021: 11 · 2020: 13 · 2019: 9 · 2018: 8 · 2017: 4
FWCI
9.23
Type
journal article
Language
en
Open access
Licence
Locations
  • Biomaterials (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • CIRM (TR3-05559 and TR1-01277 to YX)
  • NIH NHLBI (R01HL113468)
  • RMW
  • NHLBI (T32HL105373)
  • Powell Foundation
  • NSF
Topics
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
Keywords
humanized mice, biomaterial biocompatibility, decellularized extracellular matrix, hydrogels, T helper cells, Th2 polarization, M2 macrophages, immune response, xenotransplantation
MeSH terms
Animals, Biocompatible Materials, Extracellular Matrix, Gene Expression Regulation, T-Lymphocytes, Helper-Inducer, Humans, Immunity, Injections, Macrophages, Cell Polarity, Hydrogel, Polyethylene Glycol Dimethacrylate, Models, Animal, Sus scrofa, Mice, Allografts, Heterografts

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