RUNX1c Regulates Hematopoietic Differentiation of Human Pluripotent Stem Cells Possibly in Cooperation with Proinflammatory Signaling
Oscar Navarro-Montero et al., STEM CELLS
Runt-related transcription factor 1 (Runx1) is a master hematopoietic transcription factor essential for hematopoietic stem cell (HSC) emergence. Runx1-deﬁcient mice die during early embryogenesis due to the inability to establish deﬁnitive hematopoiesis. Here, we have used human pluripotent stem cells (hPSCs) as model to study the role of RUNX1 in human embryonic hematopoiesis. Although the three RUNX1 isoforms a, b, and c were induced in CD451 hematopoietic cells, RUNX1c was the only isoform induced in hematoendothelial progenitors (HEPs)/hemogenic endothelium. Constitutive expression of RUNX1c in human embryonic stem cells enhanced the appearance of HEPs, including hemogenic (CD431) HEPs and promoted subsequent differentiation into blood cells. Conversely, specific deletion of RUNX1c dramatically reduced the generation of hematopoietic cells from HEPs, indicating that RUNX1c is a master regulator of human hematopoietic development. Gene expression proﬁling of HEPs revealed aRUNX1c-induced proinﬂammatory molecular signature, supporting previous studies demonstrating proinﬂammatory signaling as a regulator of HSC emergence. Collectively, RUNX1c orchestrates hematopoietic speciﬁcation of hPSCs, possibly in cooperation with proinﬂammatory signaling.
Acceleration of Fracture Healing by Overexpression of Basic Fibroblast Growth Factor in the Mesenchymal Stromal Cells
Hongliang Zhang et al., STEM CELLS Translational Medicine
Mesenchymal stem cells engineered to express basic fibroblast growth factor may provide a cell-based treatment for fracture repair that provides an environment rich in stem cells, growth factors, and bone matrix proteins over a short time, thereby promoting bone regeneration.
The Wnt5a Receptor, Receptor Tyrosine Kinase‐Like Orphan Receptor 2, Is a Predictive Cell Surface Marker of Human Mesenchymal Stem Cells with an Enhanced Capacity for Chondrogenic Differentiation
Sally C. Dickinson et al., STEM CELLS
Mesenchymal stem cells (MSCs) can be turned into cartilage-forming cells. However, these stem cells vary from one donor to the other in their capacity to form cartilage and they lose this capacity all together if they are grown for too long in the laboratory. A marker protein on the surface of the stem cells might be used to predict which of them are best able to make cartilage. The authors generated clones of MSCs and showed that some of the clones are very good at making cartilage and some very poor at doing so. Through comparison of these clones, a protein was identified, ROR2, that is present at higher levels on those MSCs that are very good at making cartilage. This new marker may help to ensure a more effective cell therapy for cartilage injuries.
Safety Profile of Good Manufacturing Practice Manufactured Interferon γ‐Primed Mesenchymal Stem/Stromal Cells for Clinical Trials
Adam J. Guess et al., STEM CELLS Translational Medicine
Mesenchymal stem/stromal cells (MSCs) are one of the most widely studied cells for the development of cellular therapies. While these cells are unequivocally safe to use in humans, the efficacy of MSCs to treat diseases has not been established. Hence, current efforts are focused on developing the technology to enhance the efficacy of MSCs. Here, we report a novel strategy to prepare MSCs that would mitigate the potential reduction of cell potency observed when infusing freshly thawed, cryopreserved cells. Additionally, we show extensive preclinical data to support the safety of interferon γ-primed MSCs, which are designed to enhance the immune modulatory potency of MSCs.
Video abstract from Dr. Cooke, et al. on his recently published STEM CELLS paper entitled, "Retinoic Acid Inducible Gene 1 Protein (RIG1)-like Receptor Pathway is Required for Efficient Nuclear Reprogramming." Read the paper here.
Video abstract from Drs. Cox, Hetz, Liao, Aertker, Ewing-Cobbs, Juranek, Savitz, Jackson, Romanowska-Pawliczek, Triolo, Dash, Pedroza, Lee, Worth, Aisiku, Choi, Holcomb, and Kitagawa on their recently published STEM CELLS paper entitled, "Treatment of Severe Adult Traumatic Brain Injury Using Bone Marrow Mononuclear Cells." Read the paper here.Video Library