Abstract

Adipose tissue possesses phenotypic gene expression characteristics that are similar to human mesenchymal stem cells (hMSCs). Nevertheless, the multilineage potential may be inhibited, and cells may not expand adequately to satisfy the requirements of Good Manufacturing Practice (cGMP). An autologous hMSC-enriched fat product would fulfil the void from a biomedical and clinical perspective. In this study, we suggest a novel mechanism using a closed system without enzymes, additives or other modifications, which will produce non-expanded, accessible material. This decentralized fat product, unlike unprocessed lipoaspirates, adequately encloses the vascular stroma with adipocytes and stromal stalks along with their vascular channels and lumina. This fat product contained hASCs and fewer hematopoietic elements such as lipoaspirates, which were digested enzymatically according to flow cytometric investigations, and molecular analysis also showed significant hASC uniformity within the cells of the stromal vascular tissue. Moreover, the fat product produced a higher quantity of hASCs similar to hMSCs in isolation with the typical characteristics of an osteogenic, chondrogenic and adipogenic lineage. Interestingly, these properties were evident in the non-enzymatic derived adipose tissue, as opposed to hASCs in isolation from the enzymatically digested lipoaspirates, suggesting that the aforementioned procedure may be an adequate alternative to regenerate and engineer tissue for the treatment of various medical conditions and promote efficient patient recovery.

Highlights

  • Human mesenchymal stem cells can renew themselves efficiently, grow rapidly and differentiate successfully, all of which make them excellent cell sources in regenerative medicine in different contexts [1]

  • Bone marrow can adequately produce Human mesenchymal stem cells (hMSCs) [2], but bone marrow collection is an invasive and painful procedure; authors have investigated the need for alternative sources such as dental pulp [3] together with fetal placental membranes [4] and adipose tissue [5,6]

  • The extensive use and manipulation of stem cells within a clinical setting has been hindered by the Good Manufacturing Practice regulations regarding “cell manufacturing” [30,31], which are not applicable according to the European Parliament and Council (EC regulation no. 1394/2007) as regards minimal manipulation

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Summary

Introduction

Human mesenchymal stem cells (hMSCs) can renew themselves efficiently, grow rapidly and differentiate successfully, all of which make them excellent cell sources in regenerative medicine in different contexts [1]. Other studies regarding cell isolation from the adipose tissue of humans and other species suggest that ASCs possess multipotent qualities such as adipocyte, chondrocyte, and osteoblast pathways [16,17,18,19] and hepatocyte, neuronal-like and pancreatic pathways [20,21,22]. The extensive use and manipulation of stem cells within a clinical setting has been hindered by the Good Manufacturing Practice regulations regarding “cell manufacturing” [30,31], which are not applicable according to the European Parliament and Council Adequate and accessible procedures are required to obtain autologous hASCs with minimal manipulation for use in clinical settings

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