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Enhanced Cranial Bone Repair with Induced Neural Crest-derived Mesenchymal Progenitors

Review of “Neural crest‐derived mesenchymal progenitor cells enhance cranial allograft integration” from STEM CELLS Translational Medicine by Stuart P. Atkinson

While on the search for a potent and ideally inexhaustible source of mesenchymal stem cells (MSCs) as a crucial component of cranial bone repair strategies [1], researchers led by Dmitriy Sheyn (Cedars‐Sinai Medical Center, Los Angeles, CA, USA) explored the potential of neural crest cell (NCC)-derived mesenchymal progenitor cells (MPCs). While these cells are usually isolated from the iliac crest or long bones and originate in the mesoderm [2], their rarity in adults and the associated ethical concerns regarding their derivation from embryonic sources represent obstacles to their widespread implementation [3, 4]. Therefore, researchers from the Sheyn lab aimed to differentiate induced pluripotent stem cells (iPSCs) generated from human dermal fibroblasts into NCCs [5, 6] and subsequently into MPCs to create iNCC-MPCs.

In their recent STEM CELLS Translational Medicine article, Gleaser et al. explored the potential of iNCC-MPCs seeded within decellularized bone allografts to support improved integration and cranial bone repair [7]. The authors now highlight iNCC-MPCs as a potentially exciting alternative to bone marrow-derived MSCs as a component of cranial bone repair strategies.

The initial in vitro characterization of fluorescently-labeled iNCC-MPCs revealed a lack of significant differences to bone-marrow-derived MSCs regarding the expression of consensus markers, differentiation, or risk of cellular transformation, thereby suggesting their suitability for in vivo evaluations. Analysis of allograft transplantation into cranial defects in immunodeficient mice following seeding with either iNCC-MPCs and MSCs demonstrated the survival of both cell types for at least eight weeks and the expression of human osteogenic markers.

Interestingly, microcomputed tomography at this stage established two different responses – while iNCC-MPCs provided for enhanced structural parameters of allografts, MSCs prompted increased bone volume. Furthermore, iNCC-MPCs and MSCs supported bone bridging at the interphase between host bone and allograft, as measured by the detection of human osteocalcin and collagen type 1 at the allograft‐host interphase. However, only iNCC-MPCs supported improvements to allograft integration and biomechanical properties (compared to MSCs or cell-free allografts), suggesting their superior ability to support cranial bone replacement following their transplantation within decellularized allografts.

Given the encouraging findings of this study and the neural crest origin of the larger of the cranial bone sections, iNCC-MPCs hold immense promise as an integral component of cranial bone repair strategies.

For more on how induced neural crest-derived mesenchymal progenitors may represent the future of cranial bone repair strategies, stay tuned to the Stem Cells Portal!


  1. Morrison DA, Kop AM, Nilasaroya A, et al., Cranial reconstruction using allogeneic mesenchymal stromal cells: A phase 1 first-in-human trial. Journal of Tissue Engineering and Regenerative Medicine 2018;12:341-348.
  2. Gitton Y, Heude É, Vieux-Rochas M, et al., Evolving maps in craniofacial development. Seminars in Cell & Developmental Biology 2010;21:301-308.
  3. Liu JA and Cheung M, Neural crest stem cells and their potential therapeutic applications. Developmental Biology 2016;419:199-216.
  4. Jiang X, Gwye Y, McKeown SJ, et al., Isolation and Characterization of Neural Crest Stem Cells Derived From In Vitro–Differentiated Human Embryonic Stem Cells. Stem Cells and Development 2008;18:1059-1071.
  5. Lee G, Chambers SM, Tomishima MJ, et al., Derivation of neural crest cells from human pluripotent stem cells. Nature Protocols 2010;5:688-701.
  6. Menendez L, Kulik MJ, Page AT, et al., Directed differentiation of human pluripotent cells to neural crest stem cells. Nature Protocols 2013;8:203-212.
  7. Glaeser JD, Behrens P, Stefanovic T, et al., Neural crest-derived mesenchymal progenitor cells enhance cranial allograft integration. STEM CELLS Translational Medicine 2021;10:797-809.