Mice engrafted with human hematopoietic stem cells support a human myeloid cell inflammatory response in vivo.
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.
Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery, University of California San Diego School of Medicine, La Jolla, California.
Andrew
A
Baird
Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery, University of California San Diego School of Medicine, La Jolla, California.
Chenliang
C
Deng
Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery, University of California San Diego School of Medicine, La Jolla, California.
Matthew H
MH
Eliceiri
Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery, University of California San Diego School of Medicine, La Jolla, California.
Fatima
F
Haghi
Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery, University of California San Diego School of Medicine, La Jolla, California.|The Key Laboratory of Medical Electrophysiology, Ministry of Education of China, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China.
Xitong
X
Dang
Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery, University of California San Diego School of Medicine, La Jolla, California.
Raul
R
Coimbra
Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery, University of California San Diego School of Medicine, La Jolla, California.
Todd W
TW
Costantini
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California.
Bruce E
BE
Torbett
Division of Trauma, Surgical Critical Care, Burns, and Acute Care Surgery, Department of Surgery, University of California San Diego School of Medicine, La Jolla, California.
Brian P
BP
Eliceiri
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005434:Flow Cytometry; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology* / Q000473:pathology*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D000072737:Myeloid-Derived Suppressor Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D014945:Wound Healing / Q000276:immunology; D014947:Wounds and Injuries / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D015850:Interleukin-6; D016209:Interleukin-8; D016753:Interleukin-10
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