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Organ Complementation highlights in vivo Contribution of PSCs to Bone-forming Cells

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Review of “In Vivo Rescue of the Hematopoietic Niche by Pluripotent Stem Cell Complementation of Defective Osteoblast Compartments” from STEM CELLS by Stuart P. Atkinson

The differentiation of pluripotent stem cells (PSCs) into osteoblasts, crucial for the formation and function of the skeletal system and the bone marrow hematopoietic niche, suffers from a testing problem. We currently lack an adequate in vitro means of functionally assessing PSC-derived osteoblasts, while in vivo ectopic bone formation-based assessments cannot evaluate how PSC-derived osteoblasts contribute to endogenous bone formation.

A new STEM CELLS study from the laboratory of Joy Y. Wu (Stanford University School of Medicine, California, USA) has recently described a new means of testing the contribution of PSCs to skeletal function in vivo: organ complementation. Previous organ complementation studies described the PSC-mediated restoration of β-cell function in mutant mice lacking a pancreas [1] and the contribution of PSCs to cardiac development [2]. Now, Chubb et al. establish that PSCs can also reconstitute the skeletal system and rescue bone marrow hematopoiesis in vivo even at low levels of contribution [3].

Organ complementation assays employed a Runx2-deficient mouse that fails to form a mineralized skeleton and hematopoietic bone marrow due to a lack of osteoblasts. However, injection of fluorescently labeled PSCs into the Runx2-deficient blastocyst permitted bone mineralization during embryo development and the rescue of the bone marrow hematopoietic microenvironment, indicating that PSCs can compensate for the loss of the osteoblast lineage. The study also noted that the level of bone mineralization increased as the percentage of PSC contribution increased; however, as little as ~40% embryo contribution of PSCs restored near-normal gross skeletal morphology in the embryos.

The authors hope that these findings will permit the evaluation of specific osteoblast lineage populations and the specific roles of signaling mediators in skeletal development and hematopoiesis. If you need to “bone up” further on PSC-derived osteoblasts and their potential, keep following the Stem Cells Portal for more exciting studies!

References

  1. Kobayashi, T., et al., Generation of rat pancreas in mouse by interspecific blastocyst injection of pluripotent stem cells. Cell 2010;142:787-99.
  2. Sturzu, A.C., et al., Fetal Mammalian Heart Generates a Robust Compensatory Response to Cell Loss. Circulation 2015;132:109-21.
  3. Chubb, R., et al., In Vivo Rescue of the Hematopoietic Niche By Pluripotent Stem Cell Complementation of Defective Osteoblast Compartments. Stem Cells 2017;35:2150-2159.