Multipotent Mesenchymal Stromal Cells from Porcine Bone Marrow, Implanted under the Kidney Capsule, form an Ectopic Focus Containing Bone, Hematopoietic Stromal Microenvironment, and Muscles

Abstract

Multipotent mesenchymal stromal cells (MSCs) are an object of intense investigation due to their therapeutic potential. MSCs have been well studied in vitro, while their fate after implantation in vivo has been poorly analyzed. We studied the properties of MSCs from the bone marrow (BM-MSC) before and after implantation under the renal capsule using a mini pig model. Autologous BM-MSCs were implanted under the kidney capsule. After 2.5 months, ectopic foci containing bones, foci of ectopic hematopoiesis, bone marrow stromal cells and muscle cells formed. Small pieces of the implant were cultivated as a whole. The cells that migrated out from these implants were cultured, cloned, analyzed and were proven to meet the most of criteria for MSCs, therefore, they are designated as MSCs from the implant—IM-MSCs. The IM-MSC population demonstrated high proliferative potential, similar to BM-MSCs. IM-MSC clones did not respond to adipogenic differentiation inductors: 33% of clones did not differentiate, and 67% differentiated toward an osteogenic lineage. The BM-MSCs revealed functional heterogeneity after implantation under the renal capsule. The BM-MSC population consists of mesenchymal precursor cells of various degrees of differentiation, including stem cells. These newly discovered properties of mini pig BM-MSCs reveal new possibilities in terms of their manipulation.

Exploring functional metabolites and proteomics biomarkers in late-preterm and natural-born pigs

“…Using animal models to simulate the physiological development of preterm infants of different gestational ages is a feasible research way to develop a treatment for preterm birth. As one of the large animal models, pigs are especially suitable for pediatric basic research and treatment development of preterm infants, such as intestinal development and diseases, material metabolism, and immune function shaping ( 38 , 39 ). Our study uniquely focuses on late-preterm and naturally-born piglets, a less explored model in the literature.…”

Prospects for the Application of Transplantation With Human Amniotic Membrane Epithelial Stem Cells in Systemic Lupus Erythematosus

“…Subsequently, numerous studies 7 , 8 have reported that allotransplantation of human BM-MSCs could effectively manage the disease and enhance the prognosis of refractory SLE patients. However, as research progresses, some scholars have discovered that although BM-MSCs are widely present in the hematopoietic microenvironment and play a crucial role in hemocytogenesis and immune regulation 9 , they exhibit dysfunction in SLE patients with reduced cytokine secretion and immune regulatory abilities, decreased proliferation and differentiation capacities, abnormal cell structure, and significantly increased intracellular oxidative stress 10 . Animal experimental studies 11 also revealed that autologous BM-MSCs from SLE mice failed to migrate to target organs after transplantation in vivo , while MSCs transplanted between allogeneic groups still exhibited donor degeneration, genetic instability, and immune rejection.…”