Using Mesenchymal Stem Cells to Boost Cord Blood Ex Vivo Expansion

[Guest guest]

[One of the principal obstacles to the use of cord stem cells is the

small volume of engraftable stem cells. Here is one effort that may

hold promise in expanding the number of stem cells that would be

available for transplanting in adults.]

Tissue Engineering

Co-culture of Umbilical Cord Blood CD34þ Cells with Human Mesenchymal

Stem Cells

Aug 2006, Vol. 12, No. 8: 2161-2170

Yue Zhang , M.Sc.

Graduate Programme in BioEngineering, National University of

Singapore, Singapore.

et al

Tissue and Therapeutic Engineering Lab, Division of Biomedical

Sciences, s Hopkins in Singapore, Singapore.

Department of Biomedical Engineering, School of Medicine, s

Hopkins University, Baltimore, land.

Insufficient numbers of hematopoietic stem cells (HSCs) and

hematopoietic progenitor cells (HPCs) sometimes limit allogenic

transplantation of umbilical cord blood (UCB). Ex vivo expansion may

overcome this limitation.

Mesenchymal stem cells (MSCs), as non-hematopoietic, well-

characterized skeletaland connective-tissue progenitor cells within

the bone marrow stroma, have been investigated as support cells for

the culture of HSCs/HPCs. MSCs are attractive for the rich

environmental signals that they provide and for immunological

compatibility in transplantation. Thus far, HSC/MSC co-cultures have

mainly been performed in 2-dimensional (2D) configuration.

We postulate that a 3-dimensional (3D) culture environment that

resembles the natural in vivo hematopoietic compartment might be more

conducive for regulating HSC expansion. In this study, we compared

the co-culture of HSCs and MSCs in 2D and 3D configurations. The

results demonstrated the benefit of MSC inclusion in HSC expansion ex

vivo.

Direct contact between MSCs and HSCs in 3D cultures led to

statistically significantly higher expansion of cord blood CD34+

cells than in 2D cultures (891- versus 545-fold increase in total

cells, 96- versus 48-fold increase of CD34+ cells, and 230- versus

150-fold increase in colony-forming cell assay [CFC]).

Engraftment assays in non-obese diabetic/severe combined

immunodeficiency mice also indicated a high success rate of

hematopoiesis reconstruction with these expanded cells.