Abstract
Adipose stem cells (ASCs) are a crucial element in bone tissue engineering (BTE). They are easy to harvest and isolate, and they are available in significative quantities, thus offering a feasible and valid alternative to other sources of mesenchymal stem cells (MSCs), like bone marrow. Together with an advantageous proliferative and differentiative profile, they also offer a high paracrine activity through the secretion of several bioactive molecules (such as growth factors and miRNAs) via a sustained exosomal release which can exert efficient conditioning on the surrounding microenvironment. BTE relies on three key elements: (1) scaffold, (2) osteoprogenitor cells, and (3) bioactive factors. These elements have been thoroughly investigated over the years. The use of ASCs has offered significative new advancements in the efficacy of each of these elements. Notably, the phenotypic study of ASCs allowed discovering cell subpopulations, which have enhanced osteogenic and vasculogenic capacity. ASCs favored a better vascularization and integration of the scaffolds, while improvements in scaffolds' materials and design tried to exploit the osteogenic features of ASCs, thus reducing the need for external bioactive factors. At the same time, ASCs proved to be an incredible source of bioactive, proosteogenic factors that are released through their abundant exosome secretion. ASC exosomes can exert significant paracrine effects in the surroundings, even in the absence of the primary cells. These paracrine signals recruit progenitor cells from the host tissues and enhance regeneration. In this review, we will focus on the recent discoveries which have involved the use of ASCs in BTE. In particular, we are going to analyze the different ASCs' subpopulations, the interaction between ASCs and scaffolds, and the bioactive factors which are secreted by ASCs or can induce their osteogenic commitment. All these advancements are ultimately intended for a faster translational and clinical application of BTE.
Highlights
Bone is a complex tissue and participates into several physiological processes, including body movements, mineral homeostasis and storage, endocrine functions, and, in the bone marrow, hematopoiesis [1, 2]
It was demonstrated that a pore dimension of 400–600 μm determines the best bone tissue formation outcomes, as evidenced by the enhanced production of bone protein and calcium deposition, and the increased total bone volume, in a porous HFIP-derived silk fibroin scaffold seeded with human ASCs (hASCs)
Rat Adipose stem cells (ASCs) transfected with a lentivirus expressing miR26a and seeded on an HA scaffold showed an upregulation of proosteogenic genes and an increased bone-forming capacity
Summary
Bone is a complex tissue and participates into several physiological processes, including body movements, mineral (calcium and phosphate) homeostasis and storage, endocrine functions, and, in the bone marrow, hematopoiesis [1, 2]. Many drawbacks could hinder good results for autograft, including their limited accessibility, a limited amount of material available, Stem Cells International and morbidity at the donor site [6, 7] To overcome these limitations, bone tissue engineering (BTE) is aimed at recreating bone substitutes that are readily available, highly biocompatible, and with a significant regenerative potential [8]. An increased fracture callus size and increased mineralization after three weeks resulted in increased bone union [34] In all these xenografts models, aside from the osteogenic differentiation of human pericytes, a paracrine effect was evident, which determined a repopulation of the defect by host cells. According to literature data, a more precise selection and expansion of cellular subpopulations, under Good Manufacturing Practice (GMP) conditions, could lead to more efficient engineering protocols
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