An engineered multicomponent bone marrow niche for the recapitulation of hematopoiesis at ectopic transplantation sites

Abstract

BackgroundBone marrow (BM) niches are often inaccessible for controlled experimentation due to their difficult accessibility, biological complexity, and three-dimensional (3D) geometry. MethodsHere, we report the development and characterization of a BM model comprising of cellular and structural components with increased potential for hematopoietic recapitulation at ectopic transplantation sites. Cellular components included mesenchymal stromal cells (MSCs) and hematopoietic stem and progenitor cells (HSPCs). Structural components included 3D β-tricalcium phosphate (β-TCP) scaffolds complemented with Matrigel or collagen I/III gels for the recreation of the osteogenic/extracellular character of native BM.ResultsIn vitro, β-TCP/Matrigel combinations robustly maintained proliferation, osteogenic differentiation, and matrix remodeling capacities of MSCs and maintenance of HSPCs function over time. In vivo, scaffolds promoted strong and robust recruitment of hematopoietic cells to sites of ectopic transplantation, vascularization, and soft tissue formation.ConclusionsOur tissue-engineered BM system is a powerful tool to explore the regulatory mechanisms of hematopoietic stem and progenitor cells for a better understanding of hematopoiesis in health and disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0234-9) contains supplementary material, which is available to authorized users.

Long-term immune reconstitution and T cell repertoire analysis after autologous hematopoietic stem cell transplantation in systemic sclerosis patients

“…Some oligoclonally expanded families were still found at long-term after transplant both in group A and B patients, indicating that either the patients residual T cells survived the conditioning or were re-infused with the graft at time of aHSCT and can persist for long term or that thymic rebound was not appropriately achieved. As thymic reactivation participate to the observed clinical response after aHSCT [8–10, 19], adjuvant therapies to support hematopoiesis and thymic output could be helpful to improve long-term clinical response [17, 20, 21]. …”

Hematopoietic Niche – Exploring Biomimetic Cues to Improve the Functionality of Hematopoietic Stem/Progenitor Cells

“…Bladergroen and collaborators, for instance, loaded heparinized collagen scaffolds with SDF‐1α and implanted these in vivo (mouse), leading to recruitment of HSPC . On the other hand, Ventura‐Ferreira and colleagues combined the use of a β‐tricalcium phosphate (TCP) scaffold, evidencing bone‐characteristic porosity, with bioactive cues, provided by ECM hydrogels and co‐culture with MSC, to promote the recruitment of hematopoietic cells and enhance the scaffold vascularization once implanted in vivo in a mice model …”

Bone marrow hematons: An access point to the human hematopoietic niche

“…Our results demonstrate that human hematons constitute BM tissue subunits containing all the cellular actors of the hematopoietic niche and that they are easy to collect and represent a unique model for understanding the interdependence between immature hematopoietic cells and the BM microenvironment. Access to human hematons provides a foundation for novel investigations such as the following: (i) to evaluate the limits of extrapolation from data obtained with mouse models, ii) to advantageously replace the ex vivo artificially reconstructed 3D models of the BM microenvironment, (iii) to evaluate the application of these structures in cell therapy and to study mechanisms such as cell egress, (iv) to produce ex vivo expansion conditions when self‐renewal is difficult to reproduce, and (v) to study oncogenesis and/or the expansion of initiating leukemia stem cells and/or the relationship between malignant clones and the microenvironment …”