Adipose-derived mesenchymal stromal cells in clinical trials: Insights from single-cell studies.

Mesenchymal Stromal Cells (MSCs) offer tremendous potential for the treatment of various diseases and their healing properties have been explored in hundreds of clinical trials. These trails primarily focus on immunological and neurological disorders, as well as regenerative medicine. Adipose tissue is a rich source of mesenchymal stromal cells and methods to obtain and culture adipose-derived MSCs (AD-MSCs) have been well established. Promising results from pre-clinical testing of AD-MSCs activity prompted clinical trials that further led to the approval of AD-MSCs for the treatment of complex perianal fistulas in Crohn's disease and subcutaneous tissue defects. However, AD-MSC heterogeneity along with various manufacturing protocols or different strategies to boost their activity create the need for standardized quality control procedures and safety assessment of the intended cell product. High-resolution transcriptomic methods have been recently gaining attention, as they deliver insight into gene expression profiles of individual cells, helping to deconstruct cellular hierarchy and differentiation trajectories, and to understand cell-cell interactions within tissues. This article presents a comprehensive overview of completed clinical trials evaluating the safety and efficacy of AD-MSC treatment, together with current single-cell studies of human AD-MSC. Furthermore, our work emphasizes the increasing significance of single-cell research in elucidating the mechanisms of cellular action and predicting their therapeutic effects.

Levels of the neuropeptide phoenixin-14 and its receptor GRP173 in the hypothalamus, ovary and periovarian adipose tissue in rat model of polycystic ovary syndrome.

Phoenixin (PNX) is a newly discovered peptide produced by proteolytic cleavage of a small integral membrane protein 20 (Smim20), which acts as an important regulator of energy homeostasis and reproduction. Since dysfunction of reproduction is characteristic in polycystic ovarian syndrome (PCOS), the role of PNX in pathogenesis of PCOS needs further investigation. The objective of this study was to determine expression of Smim20, PNX-14 and its receptor GRP173 in the hypothalamus, ovary and periovarian adipose tissue (PAT) of letrozole induced PCOS rats. Phosphorylation of extracellular signal-regulated kinase (ERK1/2), protein kinases A (PKA) and B (Akt) were also estimated. We observed that PCOS rats had high weight gain and a number of ovarian cyst, high levels of testosterone, luteinizing hormone and PNX-14, while low estradiol. Smim20 mRNA expression was higher in the ovary and PAT, while PNX-14 peptide production was higher only in the ovary of PCOS rat. Moreover, in PCOS rats Gpr173 level was lower in PAT but at the protein level increased only in the ovary. Depending on the tissues, kinases phosphorylation were significantly differ in PCOS rats. Our results showed higher levels of PNX-14 in PCOS rats and indicated some novel findings regarding the mechanisms of PCOS pathophysiology.