A Preview of Selected Articles.

The gradual breakdown of joint cartilage and the underlying bone leads to the onset of osteoarthritis (OA), a prevalent form of arthritis that affects millions of people worldwide. OA represents a common cause of disability in the elderly population 1, causing serious deterioration in patients’ quality of life and generating significant cost burdens. The development and testing of new regenerative strategies, such as autologous mesenchymal stem cell (MSC)‐based treatments aimed at repairing cartilage or bone, requires a suitable model system, and OA research commonly employs canine models 2. As the prevalence of the disease reaches 20% in the adult canine population 3, both humans and canine patients could benefit greatly from the development of novel cost‐effective therapies. In our first Featured Article this month from Stem Cells Translational Medicine, researchers from the laboratory of Offer Zeira now demonstrate the safety, feasibility, and benefits of single intra‐articular injections of autologous microfragmented adipose tissue (MFAT) in a canine model of OA in what could represent a time sparing and cost‐effective treatment approach 4. In a Related Article from Stem Cells, Taheem et al. describe how exposure of human bone marrow‐derived MSCs (hBM‐MSC) to a hypoxia‐mimetic induces a chondrocytic expression profile, thereby providing an appealing means to enhance the regeneration of lost cartilage and inhibit progression to OA 5.

The devastating consequences of spinal cord injury (SCI) have also prompted the development of stem cell‐based therapeutics to provide trophic support and replace lost cells in the hope of returning functional independence to those affected. As a means to replace lost cells and provide neurotrophic support, many approaches involve the application of neural stem/progenitor cells 6; however, studies have yet to report more than a very limited level of functional recovery. The reasons for muted regenerative responses may relate to innate “insufficiencies” of the specific stem/progenitor cell population used 7 or poor preservation of the damaged tissue and low survival of host neurons 8. In our second Featured Article from Stem Cells Translational Medicine, Nagoshi et al. now report on the direct generation of myelinating oligodendrogenic tripotent neural progenitor cells (oNPCs) from patient‐derived somatic bone marrow cells and their application as an enhanced approach for functional recovery post‐SCI 9. In a Related Article from Stem Cells, Uezono et al. demonstrate how the combination of antihigh mobility group box‐1 (HMGB1) antibody treatment and the transplantation of neural stem cells derived from human induced pluripotent stem cells (hiPSC‐NSCs) can provide significant locomotion recovery following SCI 10.

Featured Articles

Successful Canine Trial Supports Autologous Adipose Tissue Treatment for Osteoarthritis

While treatment with MSCs derived from adipose tissue represents a promising strategy for OA, the regulatory pressures and elevated costs associated with purified and in vitro expanded stem cell populations has increased the relevance of minimally manipulated tissue‐based approaches. In the hope of developing a rapid and straightforward therapy for human OA patients, researchers from the laboratory of Offer Zeira (San Michele Veterinary Hospital, Tavazzano con Villavesco, Italy) recently trialed autologous MFAT in a canine model of spontaneous OA. In their new Stem Cells Translational Medicine article, the authors obtained the pericyte/MSC‐rich MFAT using a minimally invasive technique in a closed system and then treated OA dogs via injection in the intra‐ and/or peri‐articular space, all in a single‐step procedure. Encouragingly, the study noted improvements in the orthopedic and owners’ scores at one and six months in the majority of the dogs treated, with no local or systemic major adverse effects observed. The authors report their one‐step MFAT‐based approach for the treatment of spontaneous OA in a canine model to be safe, feasible, and effective, and given the time sparing and cost‐effective nature of this approach, this trial may represent a significant step toward an effective OA therapy for both human and canine patients.

DOI: https://doi.org/10.1002/sctm.18-0020

Boosting Recovery from SCI with Oligodendrogenic Neural Progenitor Cells

The transplantation of NPCs following traumatic SCI can promote recovery via neuroprotection and tripotential differentiation into neurons, astrocytes, and oligodendrocytes. Oligodendrocytes play an essential role in creating the myelin sheath and provide support and insulation to axons in the central nervous system; therefore, oligodendrocytes likely play a critical role in recovery from SCI. However, studies have discovered that the proportion of engrafted human NPCs differentiating into oligodendrocytes remains very low. To solve this problem, the laboratory of Michael G. Fehlings (University of Toronto, Ontario, Canada) directly derived tripotential oNPCs from patient bone marrow cell samples and assessed their function in a rat model of SCI. Nagoshi et al. report in Stem Cells Translational Medicine that transplanted oNPCs displayed enhanced rostrocaudal migrational capabilities and a high propensity for oligodendrocyte differentiation. Encouragingly, these improvements combined to promote tissue sparing, axonal remyelination, and the recovery of motor function without signs of tumorigenesis, and the authors hope that oNPCs will soon help to reduce the devastating physical, social, and financial consequences of SCI in human patients.

DOI: https://doi.org/10.1002/sctm.17-0269

Related Articles

Enhanced Chondrogenesis by Bone Marrow MSCs May Inhibit Progression to Osteoarthritis

Hypoxia, or low oxygen tension, plays a controlling role in the chondrogenic differentiation of MSCs, and harnessing this knowledge may permit the construction of new and improved means to repair articular cartilage lesions and inhibit progress to OA. Recent research published in Stem Cells from the laboratory of Eileen Gentleman (King's College London, UK) has provided evidence that compounds mimicking hypoxia, via the stabilization of the hypoxia‐inducible factor (HIF)‐1α transcription factor, can enhance the chondrogenic potential of hBM‐MSCs. Taheem et al. discovered that treatment with dimethyloxalylglycine (DMOG), a 2‐oxoglutarate analog, promoted the upregulation of HIF complex target genes and induced a chondrogenic expression profile in hBM‐MSCs. Compounds such as DMOG mimic hypoxia via competitive inhibition of the prolyl hydroxylase 2 (PH2) and factor inhibiting HIF (FIH) hydroxylases that regulate HIF‐1α. Of note, hypoxia mimetics that chelate or compete with divalent iron (such as desferrioxamine or cobalt chloride) did not support a chondrogenic‐like profile in hBM‐MSCs. Overall, the authors propose a central role for DMOG in future cartilage tissue engineering strategies as an effective approach to inhibit progress to OA.

DOI: https://doi.org/10.1002/stem.2844

New hiPSC‐NSC‐Based Combination Therapy Provides Enhances Functional Recovery after SCI

Besides its role as an important chromatin‐associated factor that organizes DNA and regulates transcription, HMGB1 plays a crucial role as a trigger for inflammatory responses to central nervous system injuries such as SCI. Interestingly, studies previously established that the antibody‐mediated neutralization of HMGB1 could improve recovery in the ischemic and injured brain. Therefore, researchers led by Kinichi Nakashima (Kyushu University, Higashi‐ku, Fukuoka, Japan) combined anti‐HMGB1 antibody administration with hiPSC‐NSC transplantation as a novel strategy to improve functional recovery after SCI. Reporting in , Uezono et al. established that treatment of an SCI model mouse with this combination preserved the lesion site by alleviating blood‐spinal cord barrier disruption and edema formation and constraining damage spread. Furthermore, this novel approach promoted connectivity between surviving host neurons and transplant‐derived neurons to enhance locomotion recovery to a more significant level when compared with treatment with hiPSC‐NSCs alone. Overall, this study demonstrates that the combination of an anti‐HMGB1 antibody and hiPSC‐NSCs represents a promising novel therapy for SCI.

DOI: https://doi.org/10.1002/stem.2802