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

Scars are a consequence of cutaneous wound healing that can be both unsightly and detrimental to the function of the tissue. Scar tissue is generated by excessive deposition of extracellular matrix tissue by wound healing fibroblasts and myofibroblasts, and although it is inferior to the uninjured skin, it is able to restore integrity to the boundary between the body and its environment. Scarring is not a necessary process to repair the dermal tissues. Rather, scar tissue forms due to specific mechanisms that occur during the adult wound healing process and are modulated primarily by the inflammatory response at the site of injury. Adult tissue-derived mesenchymal stem cells, which participate in normal wound healing, are trophic mediators of tissue repair. These cells participate in attenuating inflammation in the wound and reprogramming the resident immune and wound healing cells to favor tissue regeneration and inhibit fibrotic tissue formation. As a result, these cells have been considered and tested as a likely candidate for a cellular therapy to promote scar-less wound healing. This review identifies specific mechanisms by which mesenchymal stem cells can limit tissue fibrosis and summarizes recent in vivo studies where these cells have been used successfully to limit scar formation.

/pdf/mesenchymal-stem-cell-therapy-for-attenuation-of-scar-1231zsyfhr.pdf

Mesenchymal stem cell therapy for attenuation of scar formation during wound healing

Elucidation of the periosteum and its regenerative potential has become a hot topic in orthopedics. Yet few review articles address the unique features of periosteum-derived cells, particularly in light of translational therapies and engineering solutions inspired by the periosteum's remarkable regenerative capacity. This review strives to define periosteum-derived cells in light of cumulative research in the field; in addition, it addresses clinical translation of current insights, hurdles to advancement, and open questions in the field. First, we examine the periosteal niche and its inhabitant cells and the key characteristics of these cells in the context of mesenchymal stem cells and their relevance for clinical translation. We compare periosteum-derived cells with those derived from the marrow niche in in vivo studies, addressing commonalities as well as features unique to periosteum cells that make them potentially ideal candidates for clinical application. Thereafter, we review the differentiation and tissue-building properties of periosteum cells in vitro, evaluating their efficacy in comparison with marrow-derived cells. Finally, we address a new concept of banking periosteum and periosteum-derived cells as a novel alternative to currently available autogenic umbilical blood and perinatal tissue sources of stem cells for today's population of aging adults who were "born too early" to bank their own perinatal tissues. Elucidating similarities and differences inherent to multipotent cells from distinct tissue niches and their differentiation and tissue regeneration capacities will facilitate the use of such cells and their translation to regenerative medicine.

https://stemcellsjournals.onlinelibrary.wiley.com/doi/pdf/10.5966/sctm.2011-0056

Concise Review: The Periosteum: Tapping into a Reservoir of Clinically Useful Progenitor Cells

Current cell-based repair strategies have proven unsuccessful for treating cartilage defects and osteoarthritic lesions, consequently advances in innovative therapeutics are required and mesenchymal stem cell-based (MSC) therapies are an expanding area of investigation. MSCs are capable of differentiating into multiple cell lineages and exerting paracrine effects. Due to their easy isolation, expansion, and low immunogenicity, MSCs are an attractive option for regenerative medicine for joint repair. Recent studies have identified several MSC tissue reservoirs including in adipose tissue, bone marrow, cartilage, periosteum, and muscle. MSCs isolated from these discrete tissue niches exhibit distinct biological activities, and have enhanced regenerative potentials for different tissue types. Each MSC type has advantages and disadvantages for cartilage repair and their use in a clinical setting is a balance between expediency and effectiveness. In this review we explore the challenges associated with cartilage repair and regeneration using MSC-based cell therapies and provide an overview of phenotype, biological activities, and functional properties for each MSC population. This paper also specifically explores the therapeutic potential of each type of MSC, particularly focusing on which cells are capable of producing stratified hyaline-like articular cartilage regeneration. Finally we highlight areas for future investigation. Given that patients present with a variety of problems it is unlikely that cartilage regeneration will be a simple “one size fits all,” but more likely an array of solutions that need to be applied systematically to achieve regeneration of a biomechanically competent repair tissue.

/pdf/adipose-bone-marrow-and-synovial-joint-derived-mesenchymal-2roahrd0qo.pdf

Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair.

Cell recruitment, migration and homing to the fracture site are essential for the inflammatory process, neovascularization, chondrogenesis, osteogenesis and ultimately bone remodeling Mesenchymal stem cells (MSCs) are required to navigate from local sources such as the periosteum and local bone marrow, and may also be recruited from the circulation and distant bone marrow While the local recruitment process may involve matrix binding and degradation, systemic recruitment may utilize extravasation, a process used by leukocytes to exit the vasculature CXCL12 (stromal cell-derived factor-1 (SDF-1)), a member of the CXC family of chemokines, is thought to have an important role in cell migration at the fracture site However, there are many molecules upregulated in the hematoma and callus that have chemotactic potential not only for inflammatory cells but also for endothelial cells and MSCs Surprisingly, there is little direct data to support their role in cell homing during bone healing Current therapeutics for bone regeneration utilize local or systemic stem cell transplantation More recently, a novel strategy that involves mobilization of large numbers of endogenous stem and progenitor cells from bone marrow into the circulation has been shown to have positive effects on bone healing A more complete understanding of the molecular mechanisms underlying cell recruitment and homing subsequent to fracture will facilitate the fine-tuning of such strategies for bone

/pdf/cxcl12-cxcr4-signaling-and-other-recruitment-and-homing-40nf2jh5z3.pdf

CXCL12/CXCR4 signaling and other recruitment and homing pathways in fracture repair

The mesengenic multipotency of cryopreserved periosteum-derived progenitor cells (PDPCs) for chondrogenesis, osteogenesis and adipogenesis was investigated Differentiation was verified using RT-PCR and histological analysis For characterization, FACS analysis was performed with specific surface markers of mesenchymal stem cells (MSCs) Among PDPCs, unsorted periosteum-derived cells (PDCs) and dermal fibroblasts, the most distinct characteristics were found to be CD9, CD105, and CD166 In addition, these markers in PDPCs were continuously maintained until passage 15 We developed a rapid method for the isolation of PDPCs that can differentiate into mesodermal lineages and provide enough cells in a short period of time for allogeneic cell therapy

Multipotency and growth characteristic of periosteum-derived progenitor cells for chondrogenic, osteogenic, and adipogenic differentiation.

Chondrogenic differentiation of human umbilical cord blood-derived multilineage progenitor cells in atelocollagen

For the ex vivo expansion of CD34+ cells, culture conditions were optimized using cytokine cocktails and media change methods. In addition, static, orbital-shake, and stirred cultures were compared. After cultivation, total cell expansion, immunophenotypes, clonogenic ability, and metabolite concentration in media were analyzed. Optimized media change methods enhanced the number of total nucleated cells (TNCs) by 600-fold (from 104 to 6 × 106 cells) in static cultures. Furthermore, intermittent orbital-shake cultures gave the highest fold increase of TNCs and CD34+/CD38− cells. These results imply that proliferation of CD34+ cells in intermittent shake cultures was more efficient than that in static cultures under optimized culture conditions.

/pdf/optimization-of-ex-vivo-hematopoietic-stem-cell-expansion-in-l2s67ijre0.pdf

Optimization of ex vivo hematopoietic stem cell expansion in intermittent dynamic cultures.

Chondrogenesis of Enhanced Green Fluorescent Protein-labelled Umbilical Cord Blood-derived Mesenchymal Stem Cells in Bioabsorbable Membrane

Chondrogenesis of Human Umbilical Cord Blood-derived Multilineage Progenitor Cells in Atelocollagen

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