Initial experimental experience of triple-knockout pig red blood cells as potential sources for transfusion in alloimmunized patients with sickle cell disease

Takayuki Yamamoto, Mohamed H. Bikhet, Marisa B. Marques, Huy Q. Nguyen, Yehua Cui, Mariyam Javed, Syed Sikandar Raza, David Ayares, Hayato Iwase, David K.C. Cooper, Hidetaka Hara

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Blood transfusion remains important in the treatment of patients with sickle cell disease (SCD). However, alloimmunization after blood transfusion is associated with patient morbidity and mortality. Triple-knockout (TKO) pigs (i.e., pigs in which the three known xenoantigens to which humans have anti-pig antibodies have been deleted) may be an alternative source of RBCs for these patients because many humans have no preformed antibodies to TKO pig RBCs (pRBCs). Methods and materials: In an in vitro study, plasma from alloimmunized (n = 12) or non-alloimmunized (n = 12) SCD patients was used to determine IgM/IgG binding to, and CDC of, TKO pRBCs. In an in vivo study, after an estimated 25% of blood volume was withdrawn from two capuchin monkeys, CFSE-labeled TKO pRBCs were transfused. Loss of TKO pRBCs was monitored by flow cytometry, and 7 weeks later, 25% of blood was withdrawn, and CFSE-labeled monkey RBCs were transfused. Results: The in vitro study demonstrated that plasma from neither alloimmunized nor non-alloimmunized SCD patients bound IgM/IgG to, or induced CDC of, TKO pRBCs. In the in vivo study, survival of TKO pRBCs in the two capuchin monkeys was of 5 and 7 days, respectively, whereas after allotransfusion, survival was >28 days. Conclusions: In conclusion, (1) in the present limited study, no antibodies were detected that cross-reacted with TKO pRBCs, and (2) TKO pigs may possibly be an alternate source of RBCs in an emergency if no human RBCs are available.

Original languageEnglish (US)
Pages (from-to)3104-3118
Number of pages15
JournalTransfusion
Volume61
Issue number11
DOIs
StatePublished - Nov 2021
Externally publishedYes

Keywords

  • capuchin monkeys
  • red blood cells
  • sickle cell disease
  • triple-knockout pigs
  • xenotransfusion

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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