TY - JOUR
T1 - Decellularised human umbilical artery as a vascular graft elicits minimal pro-inflammatory host response ex vivo and in vivo
AU - Ahlmann, Alexander Høgsted
AU - Fang, Shu
AU - Mortensen, Sussi Bagge
AU - Andersen, Line Weis
AU - Pedersen, Pernille Gejl
AU - Juel Callesen, Johanne
AU - Bak, Sara Thornby
AU - Lambertsen, Kate Lykke
AU - Andersen, Ditte Caroline
PY - 2021/8/1
Y1 - 2021/8/1
N2 - Small diameter (<6 mm) vessel grafts still pose a challenge for scientists worldwide. De-cellularised umbilical artery (dUA) remains promising as small diameter tissue engineered vascular graft (TEVG), yet their immunogenicity remains unknown. Herein, we evaluated the host immune responses, with a focus on the innate part, towards human dUA implantation in mice, and con-firmed our findings in an ex vivo allogeneic human setup. Overall, we did not observe any differ-ences in the number of circulating white blood cells nor the number of monocytes among three groups of mice (1) dUA patch; (2) Sham; and (3) Mock throughout the study (day −7 to 28). Likewise, we found no difference in systemic inflammatory and anti‐inflammatory cytokine levels between groups. However, a massive local remodelling response with M2 macrophages were observed in the dUA at day 28, whereas M1 macrophages were less frequent. Moreover, human monocytes from allogeneic individuals were differentiated into macrophages and exposed to lyophilised dUA to maximize an eventual M1 response. Yet, dUA did not elicit any immediate M1 response as determined by the absence of CCR7 and CXCL10. Together this suggests that human dUA elicits a minimal pro‐inflammatory response further supporting its use as a TEVG in an allogeneic setup.
AB - Small diameter (<6 mm) vessel grafts still pose a challenge for scientists worldwide. De-cellularised umbilical artery (dUA) remains promising as small diameter tissue engineered vascular graft (TEVG), yet their immunogenicity remains unknown. Herein, we evaluated the host immune responses, with a focus on the innate part, towards human dUA implantation in mice, and con-firmed our findings in an ex vivo allogeneic human setup. Overall, we did not observe any differ-ences in the number of circulating white blood cells nor the number of monocytes among three groups of mice (1) dUA patch; (2) Sham; and (3) Mock throughout the study (day −7 to 28). Likewise, we found no difference in systemic inflammatory and anti‐inflammatory cytokine levels between groups. However, a massive local remodelling response with M2 macrophages were observed in the dUA at day 28, whereas M1 macrophages were less frequent. Moreover, human monocytes from allogeneic individuals were differentiated into macrophages and exposed to lyophilised dUA to maximize an eventual M1 response. Yet, dUA did not elicit any immediate M1 response as determined by the absence of CCR7 and CXCL10. Together this suggests that human dUA elicits a minimal pro‐inflammatory response further supporting its use as a TEVG in an allogeneic setup.
KW - Decellularisation
KW - Human umbilical artery
KW - Innate immunity
KW - Macrophage M1 and M2 responses
KW - Tissue engineered vascular grafting
U2 - 10.3390/ijms22157981
DO - 10.3390/ijms22157981
M3 - Journal article
C2 - 34360744
SN - 1661-6596
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 15
M1 - 7981
ER -