Strategies for regeneration of the bone using porcine adult adipose-derived mesenchymal stem cells (original) (raw)

Adipose-derived mesenchymal cells for bone regereneration: State of the art

2013

Adipose tissue represents a hot topic in regenerative medicine because of the tissue source abundance, the relatively easy retrieval, and the inherent biological properties of mesenchymal stem cells residing in its stroma. Adipose-derived mesenchymal stem cells (ASCs) are indeed multipotent somatic stem cells exhibiting growth kinetics and plasticity, proved to induce efficient tissue regeneration in several biomedical applications. A defined consensus for their isolation, classification, and characterization has been very recently achieved. In particular, bone tissue reconstruction and regeneration based on ASCs has emerged as a promising approach to restore structure and function of bone compromised by injury or disease. ASCs have been used in combination with osteoinductive biomaterial and/or osteogenic molecules, in either static or dynamic culture systems, to improve bone regeneration in several animal models. To date, few clinical trials on ASC-based bone reconstruction have been concluded and proved effective. The aim of this review is to dissect the state of the art on ASC use in bone regenerative applications in the attempt to provide a comprehensive coverage of the topics, from the basic laboratory to recent clinical applications.

Comparison of bone regenerative capacity of donor-matched human adipose–derived and bone marrow mesenchymal stem cells

Cell and Tissue Research, 2020

Adipose-derived stem cells (ASC) have been used as an alternative to bone marrow mesenchymal stem cells (BMSC) for bone tissue engineering. However, the efficacy of ASC in bone regeneration in comparison with BMSC remains debatable, since inconsistent results have been reported. Comparing ASC with BMSC obtained from different individuals might contribute to this inconsistency in results. Therefore, this study aimed to compare the bone regenerative capacity of donor-matched human ASC and BMSC seeded onto poly(l-lactide-co-ε-caprolactone) scaffolds using calvarial bone defects in nude rats. First, donor-matched ASC and BMSC were seeded onto the co-polymer scaffolds to evaluate their in vitro osteogenic differentiation. Seeded scaffolds and scaffolds without cells (control) were then implanted in calvarial defects in nude rats. The expression of osteogenesis-related genes was examined after 4 weeks. Cellular activity was investigated after 4 and 12 weeks. Bone formation was evaluated r...

Bone regeneration with autologous adipose-derived mesenchymal stem cells: A reliable experimental model in rats

MethodsX, 2020

The adult mesenchymal stem cell (MSC) has been proposed to be the definitive tool in regenerative medicine due to its multi-differentiation potential and expansion capacity ex vivo. The use of MSCs on bone regeneration has been assessed in several studies, obtaining promising results. However, the endless combinations that can be tested and the heterogeneity in the experimental conditions become a drawback when comparing results between authors. Moreover, it is very hard to find autologous studies using adipose-derived MSCs (AD-MSC) in rodents, which is the most used preclinical animal model. In this article an experimental model for basic bone tissue engineering research is described and justified, on which adult AD-MSCs are safely isolated from the rat dorsal interscapular fat pad, allowing ex vivo expansion and autogenous orthotopic reimplantation in a bilateral mandibular bone defect made in the same animal. This reliable and reproducible model provides a simple way to perform basic experimentation studies in a small animal model using autologous MSC for bone regeneration or cell therapy techniques prior to improve the research on large animal models. • Predictable and safe harvest of adipose-derived MSC. No need of animal sacrifice. • Allows for autologous studies with the most frequently used animal model: the rat. No need of allogeneic or human MSC use and, therefore, immunological concerns are avoided. • Bilateral mandibular critical size defect to allow direct control/experimental comparison.

Tissue Constructs with Human Adipose-Derived Mesenchymal Stem Cells to Treat Bone Defects in Rats

Materials

The use of porous scaffolds created by additive manufacturing is considered a viable approach for the regeneration of critical-size bone defects. This paper investigates the xenotransplantation of polycaprolactone (PCL) tissue constructs seeded with differentiated and undifferentiated human adipose-derived mesenchymal stem cells (hADSCs) to treat calvarial critical-sized defect in Wistar rats. PCL scaffolds without cells were also considered. In vitro and in vivo biological evaluations were performed to assess the feasibility of these different approaches. In the case of cell seeded scaffolds, it was possible to observe the presence of hADSCs in the rat tissue contributing directly (osteoblasts) and indirectly (stimulation by paracrine factors) to tissue formation, organization and mineralization. The presence of bone morphogenetic protein-2 (BMP-2) in the rat tissue treated with cell-seeded PCL scaffolds suggests that the paracrine factors of undifferentiated hADSC cells could stim...

Tissue engineering of bone: Clinical observations with adipose-derived stem cells, resorbable scaffolds, and growth factors

Annals of maxillofacial surgery, 2012

Tissue engineering offers a simple, nonallergenic, and viable solution for the reconstruction of human tissues such as bone. With deeper understanding of the stem cell's pathobiology, the unique properties of these tissues can be effectively harnessed for the benefit of the patients. A primary source of mesenchymal stem cells (MSCs) for bone regeneration is from adipose tissue to provide adipose-derived stem cells (ASCs). The interdependency between adipogenesis and osteogenesis has been well established. The objective of this article is to present the preliminary clinical observation with reconstruction of craniofacial osseous defects larger than critical size with ASC. Patients with large craniofacial osseous defects only were included in this study. Autogenous fat from the anterior abdominal wall of the patients was harvested from 23 patients, taken to a central tissue banking laboratory and prepared. All patients were reconstructed with ASCs, resorbable scaffolds, and growth...

Generation of Bone Tissue Using Adipose Tissue-derived Stem Cells

Bezmialem Science, 2021

Bone grafts and even bone substitutes do not meet all of the requirements of bony reconstructions. The aim of this study was to generate bone tissue from autologous adipose tissue-derived mesenchymal stem cells (ATDMSCs) and decellularised bone allografts. Methods: A 1.5 cm bone defect developed in the middle third of the rabbit's ulna. Reconstructions were carried out using miniplate and screws and interpositional autogenous bone grafts according to the designs of the groups: (1) No touch, (2) cryopreserved, (3) decellularised and (4) ATDMSCs-implanted decellularised bones. Before implantation, ATDMSCs in the last group were labelled with Q-dot and identified microscopically.

Adipose-derived stem cell therapies for bone regeneration

Expert Opinion on Biological Therapy

Introduction: Cell-based therapies exploit the heterogeneous and self-sufficient biological environment of stem cells to restore, maintain and improve tissue functions. Adipose-derived stem cells (ASCs) are, to this aim, promising cell types thanks to advantageous isolation procedures, growth kinetics, plasticity and trophic properties. Specifically, bone regeneration represents a suitable, though often challenging, target setting to test and apply ASC-based therapeutic strategies. Areas covered: ASCs are extremely plastic and secrete bioactive peptides that mediate paracrine functions, mediating their trophic actions in vivo. Numerous preclinical studies demonstrated that ASCs improve bone healing. Clinical trials are ongoing to validate the clinical feasibility of these approaches. This review is intended to define the state-of-the-art on ASCs, encompassing the biological features that make them suitable for bone regenerative strategies, and to provide an update on existing preclinical and clinical applications. Expert opinion: ASCs offer numerous advantages over other stem cells in terms of feasibility of clinical translation. Data obtained from in vivo experimentation are encouraging, and clinical trials are ongoing. More robust validations are thus expected to be achieved during the next few years, and will likely pave the way to optimized patient-tailored treatments for bone regeneration.

Isolation, characterization and osteogenic differentiation of adipose-derived stem cells: from small to large animal models

Cell and Tissue Research, 2009

One of the most important issues in orthopaedic surgery is the loss of bone resulting from trauma, infections, tumours or congenital deficiency. In view of the hypothetical future application of mesenchymal stem cells isolated from human adipose tissue in regenerative medicine, we have analysed and characterized adiposederived stem cells (ASCs) isolated from adipose tissue of rat, rabbit and pig. We have compared their in vitro osteogenic differentiation abilities for exploitation in the repair of critical osteochondral defects in autologous preclinical models. The number of pluripotent cells per millilitre of adipose tissue is variable and the yield of rabbit ASCs is lower than that in rat and pig. However, all ASCs populations show both a stable doubling time during culture and a marked clonogenic ability. After exposure to osteogenic stimuli, ASCs from rat, rabbit and pig exhibit a significant increase in the expression of osteogenic markers such as alkaline phosphatase, extracellular calcium deposition, osteocalcin and osteonectin. However, differences have been observed depending on the animal species and/ or differentiation period. Rabbit and porcine ASCs have been differentiated on granules of clinical grade hydroxyapatite (HA) towards osteoblast-like cells. These cells grow and adhere to the scaffold, with no inhibitory effect of HA during osteo-differentiation. Such in vitro studies are necessary in order to select suitable pre-clinical models to validate the use of autologous ASCs, alone or in association with proper biomaterials, for the repair of critical bone defects.

Mesenchymal stem cells from human adipose tissue and bone repair: a literature review

Biotechnology Research and Innovation, 2018

Mesenchymal stem cells (MSCs) emerge as potential tools for treatment of various diseases. Isolation methods and tissue of origin are important factors that determine the amount of obtained cells and their ability to differentiate. MSCs can be isolated from adipose tissue (ADSCs), bone marrow (BMSCs) or umbilical cord (UC-MSCs), and its characterization must follow the criteria required by the International Society for Cellular Therapy. Osteogenic differentiation capacity of ADSCs can still vary according to the culture medium used, as well as by adding factors that can alter signaling pathways and enhance bone differentiation. In addition, nanotechnology has also been used to increase osteoblastic induction and differentiation. ADSCs enhanced the prospect of treatment in different diseases, and in regenerative medicine, these cells can also be associated with different biomaterials. There is a great progress in studies with ADSCs, mainly because it is easy to access, which makes bioengineering techniques for bone tissue feasible.