TY - JOUR
T1 - Interindividual heterogeneity affects the outcome of human cardiac tissue decellularization
AU - Tenreiro, Miguel F.
AU - Almeida, Henrique V.
AU - Calmeiro, Tomás
AU - Fortunato, Elvira
AU - Ferreira, Lino
AU - Alves, Paula M.
AU - Serra, Margarida
N1 - Funding Information:
The work here presented was funded by Fundação para a Ciência e Tecnologia (FCT) projects NETDIAMOND (SAICTPAC/0047/2015), financially supported by FEEI-Lisboa2020 and FCT/POCI-01-0145-FEDER-016385, and MetaCardio (PTDC/BTM-SAL/32566/2017); iNOVA4Health-UIDB/04462/2020 and UIDP/04462/2020, a program financially supported by FCT/Ministério da Ciência, Tecnologia e Ensino Superior, through national funds; and EU-funded projects BRAV3 (H2020, ID:874827), ERAatUC (ID: 669088) and Twinning RESETageing (ID: 952266). HVA was financed by FCT Grant SFRH/BPD/120595/2016.
PY - 2021/12
Y1 - 2021/12
N2 - The extracellular matrix (ECM) of engineered human cardiac tissues corresponds to simplistic biomaterials that allow tissue assembly, or animal derived off-the-shelf non-cardiac specific matrices. Decellularized ECM from human cardiac tissue could provide a means to improve the mimicry of engineered human cardiac tissues. Decellularization of cardiac tissue samples using immersion-based methods can produce acceptable cardiac ECM scaffolds; however, these protocols are mostly described for animal tissue preparations. We have tested four methods to decellularize human cardiac tissue and evaluated their efficiency in terms of cell removal and preservation of key ECM components, such as collagens and sulfated glycosaminoglycans. Extended exposure to decellularization agents, namely sodium dodecyl sulfate and Triton-X-100, was needed to significantly remove DNA content by approximately 93% in all human donors. However, the biochemical composition of decellularized tissue is affected, and the preservation of ECM architecture is donor dependent. Our results indicate that standardization of decellularization protocols for human tissue is likely unfeasible, and a compromise between cell removal and ECM preservation must be established in accordance with the scaffold’s intended application. Notwithstanding, decellularized human cardiac ECM supported human induced pluripotent-derived cardiomyocyte (hiPSC-CM) attachment and retention for up to 2 weeks of culture, and promoted cell alignment and contraction, providing evidence it could be a valuable tool for cardiac tissue engineering.
AB - The extracellular matrix (ECM) of engineered human cardiac tissues corresponds to simplistic biomaterials that allow tissue assembly, or animal derived off-the-shelf non-cardiac specific matrices. Decellularized ECM from human cardiac tissue could provide a means to improve the mimicry of engineered human cardiac tissues. Decellularization of cardiac tissue samples using immersion-based methods can produce acceptable cardiac ECM scaffolds; however, these protocols are mostly described for animal tissue preparations. We have tested four methods to decellularize human cardiac tissue and evaluated their efficiency in terms of cell removal and preservation of key ECM components, such as collagens and sulfated glycosaminoglycans. Extended exposure to decellularization agents, namely sodium dodecyl sulfate and Triton-X-100, was needed to significantly remove DNA content by approximately 93% in all human donors. However, the biochemical composition of decellularized tissue is affected, and the preservation of ECM architecture is donor dependent. Our results indicate that standardization of decellularization protocols for human tissue is likely unfeasible, and a compromise between cell removal and ECM preservation must be established in accordance with the scaffold’s intended application. Notwithstanding, decellularized human cardiac ECM supported human induced pluripotent-derived cardiomyocyte (hiPSC-CM) attachment and retention for up to 2 weeks of culture, and promoted cell alignment and contraction, providing evidence it could be a valuable tool for cardiac tissue engineering.
UR - http://www.scopus.com/inward/record.url?scp=85117734235&partnerID=8YFLogxK
U2 - 10.1038/s41598-021-00226-5
DO - 10.1038/s41598-021-00226-5
M3 - Article
C2 - 34675273
AN - SCOPUS:85117734235
SN - 2045-2322
VL - 11
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 20834
ER -