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iPSC-MSCs: A New and Effective Means to Repair Bone Defects

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Review of “Human iPSCs Differentiate Into Functional MSCs and Repair Bone Defects” from Stem Cells Translational Medicine by Stuart P. Atkinson

The ability of mesenchymal stem cells (MSCs) to differentiate towards osteogenic lineages combined with their easy isolation from multiple tissue sources makes them the go-to cell for autologous bone regeneration and repair. However, some research suggests that the regenerative potential of MSCs declines with age [1-3] meaning that MSCs derived from elderly patients, the demographic who suffer greatly from bone injuries, may not be optimally functional.

This problem has led the team of Zulma Gazit (Cedars-Sinai Medical Center, Los Angeles, USA) to assess another strategy: producing MSCs from induced pluripotent stem cells (iPSCs). In a new Stem Cells Translational Medicine study, Sheyn et al now report that iPSC-derived MSCs can regenerate bone defects in mice in a similar manner to bone marrow (BM)-derived MSCs [4]. Could iPSC-MSCs represent a new and more effective means to repair bone defects in humans?

Initial comparisons compared healthy human BM-MSCs with two different populations of cells derived from embryoid body (EB)-based transforming growth factor (TGF)-β driven differentiation of iPSCs. The early population of cells grew from EBs which attached to tissue culture plastic (aiMSCs), while the late population of cells grew from EBs which stayed unattached during transfer (tiMSCs).

Both iMSC populations maintained a significantly increased proliferation rate compared with BM-MSCs over the first 8 passages and displayed some alterations to mesenchymal markers and overall gene expression. Nevertheless, all three MSC populations possessed similar in vitro multilineage differentiation potential, except for aiMSCs which displayed a greater osteogenic potential compared with tiMSCs or BM-MSCs.

Previous studies by the same authors found that BMP6 overexpression in BM-MSCs could promote bone formation in vivo, and so, the authors sought to assess the “bone-boosting” effect of BMP6 in their newly derived iMSCs as well as the control MSCs. Injection of BMP6-overexpressing MSCs into thigh musculature of mice (ectopic injections) mediated bone formation for BM-MSCs and aiMSCs, but not tiMSCs (See attached figure). Meanwhile, injection of all three BMP6-overexpressing MSC types into radial bone defects (orthotopic) led to the regeneration of bone and defect repair, although tiMSCs induced the highest bone formation volume.

Great news! MSCs derived from iPSCs, whether they be early-birds or late-comers, seem to have a potent ability to repair bone defects in a mouse model. This new strategy could avoid both the deleterious in vitro expansion of MSCs and the risk associated with MSC harvest from elderly patients and thereby lead to the generation of safer and more effective MSC-based therapies for bone repair and regeneration. 

It seems that iPSC-MSCs may indeed be a new and effective means to repair bone defects!

References

  1. de Girolamo L, Lopa S, Arrigoni E, et al. Human adipose-derived stem cells isolated from young and elderly women: their differentiation potential and scaffold interaction during in vitro osteoblastic differentiation. Cytotherapy 2009;11:793-803.
  2. Yukata K, Xie C, Li TF, et al. Aging periosteal progenitor cells have reduced regenerative responsiveness to bone injury and to the anabolic actions of PTH 1-34 treatment. Bone 2014;62:79-89.
  3. Lavasani M, Robinson AR, Lu A, et al. Muscle-derived stem/progenitor cell dysfunction limits healthspan and lifespan in a murine progeria model. Nat Commun 2012;3:608.
  4. Sheyn D, Ben-David S, Shapiro G, et al. Human Induced Pluripotent Stem Cells Differentiate Into Functional Mesenchymal Stem Cells and Repair Bone Defects. Stem Cells Translational Medicine 2016;5:1447-1460.