JP-2022523460-A5 -

Dates

Publication Date

20221226

Application Date

20200115

Description

Conclusion: These results demonstrate a reduction in fibrous tissue formation and an increase in myometrial regeneration after hUC-MSC sheet transplantation into repaired uterine incisions in rat uteruses, compared to controls without hUC-MSC sheet transplantation. Therefore, the hUC-MSC sheets described herein have the potential to improve uterine scar healing and reduce the morbidity associated with abnormal uterine scar formation. The present invention includes, for example, the following embodiments: [Embodiment 1] A method for reducing the formation of fibrous tissue in a target uterus, comprising the step of applying a mesenchymal stem cell (MSC) sheet to the target uterus, wherein the MSC sheet comprises one or more layers of aggregated confluent mesenchymal stem cells (MSCs), and by applying the MSC sheet to the uterus, the formation of fibrous tissue in the uterus is reduced compared to a uterus to which the MSC sheet is not applied. [Embodiment 2] A method for increasing myometrial regeneration in a target uterus, comprising the step of applying a mesenchymal stem cell (MSC) sheet to the target uterus, wherein the MSC sheet comprises one or more layers of aggregated confluent mesenchymal stem cells (MSCs), and the application of the MSC sheet to the uterus increases myometrial regeneration compared to a uterus to which the MSC sheet is not applied. [Embodiment 3] The method according to Embodiment 1 or 2, wherein the MSC sheet is applied to the incision site of the uterus. [Embodiment 4] The method according to Embodiment 1, wherein by applying the MSC sheet to the uterus, the fibrous surface area of the uterus is reduced by at least 20% compared to a uterus to which the MSC sheet is not applied. [Embodiment 5] The method according to Embodiment 1 or 2, wherein the MSC sheet is essentially made of MSC. [Embodiment 6] The method according to Embodiment 1 or 2, wherein the cell sheet includes an extracellular matrix. [Embodiment 7] The method according to Embodiment 6, wherein the extracellular matrix comprises one or more proteins selected from the group consisting of fibronectin, laminin, and collagen. [Embodiment 8] The method according to Embodiment 1 or 2, wherein the cell sheet comprises a cell adhesion protein and a cell binding protein. [Embodiment 9] The method according to Embodiment 8, wherein the cell junction protein is selected from the group consisting of vinculin, integrin-β1, connexin 43, β-catenin, integrin-linked kinase, and N-cadherin. [Embodiment 10] The method according to any one of Embodiments 1 to 9, wherein the MSCs are isolated from the subepithelial layer of human umbilical cord tissue. [Embodiment 11] The method according to any one of Embodiments 1 to 10, wherein the MSC expresses a protein selected from CD44 and CD90. [Embodiment 12] The method according to any one of Embodiments 1 to 11, wherein the MSC expresses a cytokine selected from the group consisting of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and interleukin-10 (IL-10). [Embodiment 13] The method according to Embodiment 12, wherein the expression of the cytokine in the cell sheet is increased compared to an MSC suspension containing an equivalent number of cells. [Embodiment 14] The method according to Embodiment 13, wherein the cell sheet expresses the cytokine for at least 10 days after transplantation into the tissue of a host organism. [Embodiment 15] The method according to any one of Embodiments 1 to 14, wherein the cell sheet expresses extracellular matrix proteins and cell-binding proteins for at least 10 days after transplantation into the tissue of a host organism. [Embodiment 16] The method according to Embodiment 15, wherein the extracellular matrix protein is selected from the group consisting of fibronectin, laminin, and collagen. [Embodiment 17] The method according to Embodiment 15, wherein the cell junction protein is selected from the group consisting of vinculin, integrin-β1, connexin 43, β-catenin, integrin-linked kinase, and N-cadherin. [Embodiment 18] The method according to any one of Embodiments 1 to 17, wherein the initial cell density of the MSCs in the cell culture support used to prepare the cell sheet is 0.5 × 10⁴ / cm² to 9 × 10⁵ / cm² . [Embodiment 19] The method according to any one of Embodiments 1 to 18, wherein the MSC does not express human leukocyte antigen-DR isotype (HLA-DR), human leukocyte antigen-DP isotype (HLA-DP), or human leukocyte antigen-DQ isotype (HLA-DQ). [Embodiment 20] The method according to any one of Embodiments 1 to 19, wherein the MSC includes microvilli and filopopods. [Embodiment 21] The method according to any one of Embodiments 1 to 20, wherein the cell sheet remains attached to the tissue of the host organism for at least 10 days after transplantation into the tissue. [Embodiment 22] The method according to any one of Embodiments 1 to 21, wherein the MSCs in the cell sheet are homogeneous and heterogeneous with re