A biotherapy based on PSCs-in-3D spheroid-ameliorated biologics depletes in vivo cancer-sustaining stem cells

Abstract

CSCs are able to survive routine anticancer procedures and peripheral-immune attack. Here we develop and detail a framework of CSC elimination governed by 3D-biologics. Pluripotent cells-engineered 3D-biologics (PMSB) and control non-3D-biologics were prepared from placenta-based somatic stem cells (PSCs) and inoculated respectively into senile hosts bearing progressive mammary, lung, colon carcinomas and melanoma. We demonstrate that PMSB evokes in vivo central-immune microenvironment with subsequent re-expression of thymosin-α1 ~ β4 in thymic cortex-medulla borderline for rapid MHC-unrestricted renewal of γδT-dominated immunocompetence. The post-renewal γδT-subsets could accurately bind and drive CSCs into apoptosis. Finally, with central/peripheral integral microenvironment renewal and TERT/Wnt/β-catenin pathway blockade, the CSC-subsets are fully depleted, leading to substantial cure of diverse tumors by PMSB inoculation (P < 0.01), yet not by non-3D-biologics. Thus, our study may contribute to open up a new avenue for tumor remission via pluripotent cells-engineered 3D-biologics addressing quick renewal of central-thymus and peripheral immune-microenvironment.

Methods and criteria for validating the multimodal functions of perinatal derivatives when used in oncological and antimicrobial applications

“…VEGF Placenta-based somatic stem cells (Zhang et al, 2015) Placental-derived adherent stromal cells (Allen et al, 2018) Umbilical cord MSCs (Bajetto et al, 2017;Lin D et al, 2017;Ciavarella et al, 2015) Wharton jelly MSCs (Kalamegam et al, 2019;Mandal et al, 2019;Subramanian et al, 2012) Umbilical cord MSCs (Dabrowski FA et al, 2017); Amniotic membrane MSCs (Dabrowski FA et al, 2017) FGFS Umbilical cord MSCs (Ciavarella et al, 2015) Wharton jelly stem cells (Kalamegam et al, 2019) MMPs Placenta derived MSCs (Choi et al, 2016) Placental-derived adherent stromal cells (Allen et al, 2018) TIMPs Umbilical cord MSCs (Ciavarella et al, 2015) Human amniotic membrane (Modaresifar et al, 2017) ANG Umbilical cord MSCs (Bajetto et al, 2017) EGF Umbilical cord MSCs (Ciavarella et al, 2015;Dabrowski FA et al, 2017); Amniotic membrane MSCs (Dabrowski FA et al, 2017) Frontiers in Bioengineering and Biotechnology frontiersin.org…”