TY - JOUR

T1 - Do Human iPSC-Derived Cardiomyocytes Cultured on PLA Scaffolds Induce Expression of CD28/CTLA-4 by T Lymphocytes?

AU - Sergeevichev, David

AU - Balashov, Victor

AU - Kozyreva, Victoria

AU - Pavlova, Sophia

AU - Vasiliyeva, Maria

AU - Romanov, Alexander

AU - Chepeleva, Elena

N1 - Funding Information: This work was carried out within the state assignment of Ministry of Health of Russian Federation (theme # 121031300224-1). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/1

Y1 - 2022/1

N2 - Many research groups have developed various types of tissue-engineered cardiac con-structs. However, the immunological properties of such artificial tissues are not yet fully understood. Previously, we developed microfiber scaffolds carrying human iPSC-derived cardiomyocytes (hiPSC-CM). In this work, we evaluated the ability of these tissue-engineered constructs to activate the expression of CD28 and CTLA-4 proteins on T lymphocytes, which are early markers of the immune response. For this purpose, electrospun PLA microfiber scaffolds were seeded with hiPSC-CM and cultured for 2 weeks. Allogeneic mononuclear cells were then co-cultured for 48 h with three groups of samples: bare scaffolds, pure cardiomyocyte culture and tissue-engineered constructs, followed by analysis of CD28/CTLA-4 expression on T lymphocytes using flow cytometry. PLA scaffolds and concanavalin A stimulation (positive control) statistically significantly increased CD28 expression on CD4+ T cells (up to 61.3% and 66.3%) CD8+ T cells (up to 17.8% and 21.7%). CD28/CTLA-4 expression was not increased when T lymphocytes were co-cultured with cardiac tissue-engineered constructs and iPSC-CM monolayers. Thus, iPSC-CM in monolayers and on PLA microfiber scaffolds did not induce T cell activation, which suggests that such cardiac constructs would not be a cause of rejection after implantation.

AB - Many research groups have developed various types of tissue-engineered cardiac con-structs. However, the immunological properties of such artificial tissues are not yet fully understood. Previously, we developed microfiber scaffolds carrying human iPSC-derived cardiomyocytes (hiPSC-CM). In this work, we evaluated the ability of these tissue-engineered constructs to activate the expression of CD28 and CTLA-4 proteins on T lymphocytes, which are early markers of the immune response. For this purpose, electrospun PLA microfiber scaffolds were seeded with hiPSC-CM and cultured for 2 weeks. Allogeneic mononuclear cells were then co-cultured for 48 h with three groups of samples: bare scaffolds, pure cardiomyocyte culture and tissue-engineered constructs, followed by analysis of CD28/CTLA-4 expression on T lymphocytes using flow cytometry. PLA scaffolds and concanavalin A stimulation (positive control) statistically significantly increased CD28 expression on CD4+ T cells (up to 61.3% and 66.3%) CD8+ T cells (up to 17.8% and 21.7%). CD28/CTLA-4 expression was not increased when T lymphocytes were co-cultured with cardiac tissue-engineered constructs and iPSC-CM monolayers. Thus, iPSC-CM in monolayers and on PLA microfiber scaffolds did not induce T cell activation, which suggests that such cardiac constructs would not be a cause of rejection after implantation.

KW - Cardiomyocytes

KW - CD28

KW - CTLA-4

KW - Differentiation

KW - Electrospinning

KW - Graft rejection

KW - Immune response

KW - IPSC

UR - http://www.scopus.com/inward/record.url?scp=85123064979&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/67c875b2-5d71-39be-9918-61eb06fe1fdb/

U2 - 10.3390/jfb13010006

DO - 10.3390/jfb13010006

M3 - Article

C2 - 35076538

AN - SCOPUS:85123064979

VL - 13

JO - Journal of Functional Biomaterials

JF - Journal of Functional Biomaterials

SN - 2079-4983

IS - 1

M1 - 6

ER -