TY - JOUR
T1 - Mice engrafted with human hematopoietic stem cells support a human myeloid cell inflammatory response in vivo
AU - Baird, Andrew
AU - Deng, Chenliang
AU - Eliceiri, Matthew H.
AU - Haghi, Fatima
AU - Dang, Xitong
AU - Coimbra, Raul
AU - Costantini, Todd W.
AU - Torbett, Bruce E.
AU - Eliceiri, Brian P.
N1 - Publisher Copyright:
© 2016 by the Wound Healing Society
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Mice engrafted with human CD34+ hematopoietic stem and progenitor cells (CD34+-HSPCs) have been used to study human infection, diabetes, sepsis, and burn, suggesting that they could be highly amenable to characterizing the human inflammatory response to injury. To this end, human leukocytes infiltrating subcutaneous implants of polyvinyl alcohol (PVA) sponges were analyzed in immunodeficient NSG mice reconstituted with CD34+-HSPCs. It was reported that human CD45+ (hCD45+) leukocytes were present in PVA sponges 3 and 7 days postimplantation and could be localized within the sponges by immunohistochemistry. The different CD45+ subtypes were characterized by flow cytometry and the profile of human cytokines they secreted into PVA wound fluid was assessed using a human-specific multiplex bead analyses of human IL-12p70, TNFα, IL-10, IL-6, IL1β, and IL-8. This enabled tracking the functional contributions of HLA-DR+, CD33+, CD19+, CD62L+, CD11b+, or CX3CR1+ hCD45+ infiltrating inflammatory leukocytes. PCR of cDNA prepared from these cells enabled the assessment and differentiation of human, mouse, and uniquely human genes. These findings support the hypothesis that mice engrafted with CD34+-HSPCs can be deployed as precision avatars to study the human inflammatory response to injury.
AB - Mice engrafted with human CD34+ hematopoietic stem and progenitor cells (CD34+-HSPCs) have been used to study human infection, diabetes, sepsis, and burn, suggesting that they could be highly amenable to characterizing the human inflammatory response to injury. To this end, human leukocytes infiltrating subcutaneous implants of polyvinyl alcohol (PVA) sponges were analyzed in immunodeficient NSG mice reconstituted with CD34+-HSPCs. It was reported that human CD45+ (hCD45+) leukocytes were present in PVA sponges 3 and 7 days postimplantation and could be localized within the sponges by immunohistochemistry. The different CD45+ subtypes were characterized by flow cytometry and the profile of human cytokines they secreted into PVA wound fluid was assessed using a human-specific multiplex bead analyses of human IL-12p70, TNFα, IL-10, IL-6, IL1β, and IL-8. This enabled tracking the functional contributions of HLA-DR+, CD33+, CD19+, CD62L+, CD11b+, or CX3CR1+ hCD45+ infiltrating inflammatory leukocytes. PCR of cDNA prepared from these cells enabled the assessment and differentiation of human, mouse, and uniquely human genes. These findings support the hypothesis that mice engrafted with CD34+-HSPCs can be deployed as precision avatars to study the human inflammatory response to injury.
UR - http://www.scopus.com/inward/record.url?scp=84990245140&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84990245140&partnerID=8YFLogxK
U2 - 10.1111/wrr.12471
DO - 10.1111/wrr.12471
M3 - Article
C2 - 27663454
AN - SCOPUS:84990245140
SN - 1067-1927
VL - 24
SP - 1004
EP - 1014
JO - Wound Repair and Regeneration
JF - Wound Repair and Regeneration
IS - 6
ER -