Evaluating Interaction of Cord Blood Hematopoietic Stem/Progenitor Cells with Functionally Integrated Three-Dimensional Microenvironments

Author:

Mokhtari Saloomeh1,Baptista Pedro M.2345,Vyas Dipen A.1,Freeman Charles Jordan1,Moran Emma1,Brovold Matthew1,Llamazares Guillermo A.1,Lamar Zanneta6,Porada Christopher D.1,Soker Shay1,Almeida-Porada Graça1

Affiliation:

1. a Wake Forest Institute for Regenerative Medicine, Winston-Salem, North Carolina, USA

2. b Instituto de Investigacion Sanitaria de Aragón (IIS Aragón), Zaragoza, Spain

3. c CIBERehd, Zaragoza, Spain

4. d Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Madrid, Spain

5. e Departamento de Bioingeniería Universidad Carlos III de Madrid, Spain Aragon Health Sciences Institute (IACS), Zaragoza, Spain

6. f Hematology Oncology, Wake Forest Health Sciences, Winston-Salem, North Carolina, USA

Abstract

Abstract Despite advances in ex vivo expansion of cord blood-derived hematopoietic stem/progenitor cells (CB-HSPC), challenges still remain regarding the ability to obtain, from a single unit, sufficient numbers of cells to treat an adolescent or adult patient. We and others have shown that CB-HSPC can be expanded ex vivo in two-dimensional (2D) cultures, but the absolute percentage of the more primitive stem cells decreases with time. During development, the fetal liver is the main site of HSPC expansion. Therefore, here we investigated, in vitro, the outcome of interactions of primitive HSPC with surrogate fetal liver environments. We compared bioengineered liver constructs made from a natural three-dimensional-liver-extracellular-matrix (3D-ECM) seeded with hepatoblasts, fetal liver-derived (LvSt), or bone marrow-derived stromal cells, to their respective 2D culture counterparts. We showed that the inclusion of cellular components within the 3D-ECM scaffolds was necessary for maintenance of HSPC viability in culture, and that irrespective of the microenvironment used, the 3D-ECM structures led to the maintenance of a more primitive subpopulation of HSPC, as determined by flow cytometry and colony forming assays. In addition, we showed that the timing and extent of expansion depends upon the biological component used, with LvSt providing the optimal balance between preservation of primitive CB HSPC and cellular differentiation.

Funder

NIH

NHLBI Biologic Specimen and Data Repository Information Coordinating Center

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,General Medicine

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