https://www.cell.com/cell-stem-cell/pdf/S1934-5909(15)00267-2.pdf

Stem Cell Therapies in Clinical Trials: Progress and Challenges

Oral surgery, oral medicine, oral pathology, oral radiology and endodontics

The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in the genetic manipulation of human ESCs, even though these cells are, theoretically, highly beneficial. Mesenchymal stem cells seem to be an ideal population of stem cells for practical regenerative medicine, because they are not subjected to the same restrictions. In particular, large number of adipose-derived stem cells (ASCs) can be easily harvested from adipose tissue. Furthermore, recent basic research and preclinical studies have revealed that the use of ASCs in regenerative medicine is not limited to mesodermal tissue but extends to both ectodermal and endodermal tissues and organs, although ASCs originate from mesodermal lineages. Based on this background knowledge, the primary purpose of this concise review is to summarize and describe the underlying biology of ASCs and their proliferation and differentiation capacities, together with current preclinical and clinical data from a variety of medical fields regarding the use of ASCs in regenerative medicine. In addition, future directions for ASCs in terms of cell-based therapies and regenerative medicine are discussed. STEM CELLS 2012;30:804–810

https://stemcellsjournals.onlinelibrary.wiley.com/doi/epdf/10.1002/stem.1076

Concise Review: Adipose‐Derived Stem Cells as a Novel Tool for Future Regenerative Medicine

The ability of the skin to repair itself after injury is vital to human survival and is disrupted in a spectrum of disorders. The process of cutaneous wound healing is complex, requiring a coordinated response by immune cells, hematopoietic cells, and resident cells of the skin. We review the classic paradigms of wound healing and evaluate how recent discoveries have enriched our understanding of this process. We evaluate current and experimental approaches to treating cutaneous wounds, with an emphasis on cell-based therapies and skin transplantation.

https://science.sciencemag.org/content/sci/346/6212/941.full.pdf

Advances in skin grafting and treatment of cutaneous wounds.

Bone fusion represents a challenge in the orthopedics practice, being especially indicated for spine disorders. Spinal fusion can be defined as the bony union between two vertebral bodies obtained through the surgical introduction of an osteoconductive, osteoinductive, and osteogenic compound. Autogenous bone graft provides all these three qualities and is considered the gold standard. However, a high morbidity is associated with the harvest procedure. Intensive research efforts have been spent during the last decades to develop new approaches and technologies for successful spine fusion. In recent years, cell and gene therapies have attracted great interest from the scientific community. The improved knowledge of both mesenchymal stem cell biology and osteogenic molecules allowed their use in regenerative medicine, representing attractive approaches to achieve bone regeneration also in spinal surgery applications. In this review we aim to describe the developing gene- and cell-based bone regenerative approaches as promising future trends in spine fusion.

https://downloads.hindawi.com/journals/tswj/2014/406159.pdf

Spinal Fusion in the Next Generation: Gene and Cell Therapy Approaches

A number of surgical techniques have been developed to promote periodontal tissue regeneration. Bone marrow-derived stem cells have also been shown to promote periodontal tissue regeneration. In this study, we sought to determine whether adipose-derived stem cells (ASCs) can promote periodontal tissue regeneration as well. ASCs were isolated from a Wistar rat, passaged twice, mixed with platelet-rich plasma (PRP) obtained from inbred rats, and implanted into the periodontal tissue defect that had been generated in the test rats. Tissue specimens were harvested after 2, 4, and 8 weeks for histological analysis. Rats that received PRP only or were not implanted served as controls. A small amount of alveolar bone regeneration was observed 2 and 4 weeks after ASC/PRP implantation. Moreover, 8 weeks after implantation, a periodontal ligament-like structure was observed along with alveolar bone. These observations suggest that ASCs can promote periodontal tissue regeneration in vivo. Because large amounts of human lipoaspirates are readily available, and their procurement induces only low morbidity, ASCs may be useful in future clinical cell-based therapy for periodontal disease.

Periodontal Tissue Regeneration with Adipose-Derived Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that were initially isolated from bone marrow. However, subsequent research has shown that other adult tissues also contain MSCs. MSCs originate from mesenchyme, which is embryonic tissue derived from the mesoderm. These cells actively proliferate, giving rise to new cells in some tissues, but remain quiescent in others. MSCs are capable of differentiating into multiple cell types including adipocytes, chondrocytes, osteocytes, and cardiomyocytes. Isolation and induction of these cells could provide a new therapeutic tool for replacing damaged or lost adult tissues. However, the biological properties and use of stem cells in a clinical setting must be well established before significant clinical benefits are obtained. This paper summarizes data on the biological properties of MSCs and discusses current and potential clinical applications.

/pdf/mesenchymal-stem-cells-isolated-from-adipose-and-other-1ag7abeq2w.pdf

Mesenchymal stem cells isolated from adipose and other tissues: basic biological properties and clinical applications.

Adipose tissue is an abundant source of mesenchymal stem cells, which have shown promise in the field of regenerative medicine. Furthermore, these cells can be readily harvested in large numbers with low donor-site morbidity. During the past decade, numerous studies have provided preclinical data on the safety and efficacy of adipose-derived stem cells, supporting the use of these cells in future clinical applications. Various clinical trials have shown the regenerative capability of adipose-derived stem cells in subspecialties of medical fields such as plastic surgery, orthopedic surgery, oral and maxillofacial surgery, and cardiac surgery. In addition, a great deal of knowledge concerning the harvesting, characterization, and culture of adipose-derived stem cells has been reported. This review will summarize data from in vitro studies, pre-clinical animal models, and recent clinical trials concerning the use of adipose-derived stem cells in regenerative medicine.

Adipose-derived stem cells: current findings and future perspectives.

Summary Background Primary tendon repair aims at increased tensile strength at the time of mobilisation. Tendon repair and regeneration using mesenchymal stem cells have been described in different studies; however, adipose-derived stem cell (ASC) use for tendon regeneration and repair has recently been taken into consideration. In this study, we sought to determine whether ASCs would be beneficial in primary tendon healing. Materials and methods Both the Achilles tendons of rabbits ( n  = 6) were incised and consequently repaired. To the left side was applied platelet-rich plasma (PRP) gel and to the right side autologous ASC-mixed PRP. The tensile strength was measured on the 4th week. The samples were taken for immunohistochemical evaluation of collagen type I, transforming growth factor beta (TGF-β) 1, 2, 3, fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF). Results The tensile strengths in control and experimental groups were found out to be 29.46 ± 3.66 and 43.06 ± 3.80 kgf. Collagen type I, FGF and VEGF levels were statistically higher, whereas TGF-β1, 2, 3 were lower in the experimental group. Conclusion ASCs enhance primary tendon healing; however, the complex interaction and the cascades by which ASCs could increase collagen type I, FGF and VEGF and decrease TGF-β levels should further be investigated.

Morikuni Tobita

Papers

Concise Review: Adipose‐Derived Stem Cells as a Novel Tool for Future Regenerative Medicine

Periodontal Tissue Regeneration with Adipose-Derived Stem Cells

Mesenchymal stem cells isolated from adipose and other tissues: basic biological properties and clinical applications.

Adipose-derived stem cells: current findings and future perspectives.

Adipose-derived stem cells enhance primary tendon repair: biomechanical and immunohistochemical evaluation.