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2015 ; 4
(6
): 625-31
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Immunobiology of fibrin-based engineered heart tissue
#MMPMID25947338
Conradi L
; Schmidt S
; Neofytou E
; Deuse T
; Peters L
; Eder A
; Hua X
; Hansen A
; Robbins RC
; Beygui RE
; Reichenspurner H
; Eschenhagen T
; Schrepfer S
Stem Cells Transl Med
2015[Jun]; 4
(6
): 625-31
PMID25947338
show ga
Different tissue-engineering approaches have been developed to induce and promote
cardiac regeneration; however, the impact of the immune system and its responses
to the various scaffold components of the engineered grafts remains unclear.
Fibrin-based engineered heart tissue (EHT) was generated from neonatal Lewis
(Lew) rat heart cells and transplanted onto the left ventricular surface of three
different rat strains: syngeneic Lew, allogeneic Brown Norway, and
immunodeficient Rowett Nude rats. Interferon spot frequency assay results showed
similar degrees of systemic immune activation in the syngeneic and allogeneic
groups, whereas no systemic immune response was detectable in the immunodeficient
group (p < .001 vs. syngeneic and allogeneic). Histological analysis revealed
much higher local infiltration of CD3- and CD68-positive cells in syngeneic and
allogeneic rats than in immunodeficient animals. Enzyme-linked immunospot and
immunofluorescence experiments revealed matrix-directed TH1-based rejection in
syngeneic recipients without collateral impairment of heart cell survival.
Bioluminescence imaging was used for in vivo longitudinal monitoring of
transplanted luciferase-positive EHT constructs. Survival was documented in
syngeneic and immunodeficient recipients for a period of up to 110 days after
transplant, whereas in the allogeneic setting, graft survival was limited to only
14 ± 1 days. EHT strategies using autologous cells are promising approaches for
cardiac repair applications. Although fibrin-based scaffold components elicited
an immune response in our studies, syngeneic cells carried in the EHT were
relatively unaffected. SIGNIFICANCE: An initial insight into immunological
consequences after transplantation of engineered heart tissue was gained through
this study. Most important, this study was able to demonstrate cell survival
despite rejection of matrix components. Generation of syngeneic human engineered
heart tissue, possibly using human induced pluripotent stem cell technology with
subsequent directed rejection of matrix components, may be a potential future
approach to replace diseased myocardium.
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