Enhancement of swine progenitor chimerism in mixed swine/human bone marrow cultures with swine cytokines.

Abstract:

OBJECTIVE:The induction of transplantation tolerance across xenogeneic barriers by bone marrow transplantation holds great promise, but engraftment of xenogeneic stem cells has been difficult to achieve. Part of this difficulty is due to species-specific differences in regulatory cytokines and elements of the stromal microenvironment, which we studied here. MATERIALS AND METHODS:We developed a system where fresh bone marrow cells from swine and human are cultured on human bone marrow stroma in order to study these limiting factors in a clinically relevant species combination. RESULTS:We report here the ability of recombinant swine interleukin (IL)-3 and c-kit ligand (KL) to specifically enhance swine hematopoietic chimerism in this system. In the absence of exogenous swine cytokines, there were about half as many swine progenitors as human progenitors at 1, 2, and 4 weeks of culture. When used alone, swine IL-3 led to a notable but transient increase in the relative ratio of swine progenitors, while addition of swine KL increased the ratio of swine progenitors only modestly and only at later time points. In contrast, when swine IL-3 and KL were added together, there was a two- to fourfold increase in the ratio of swine to human progenitors at all times tested. CONCLUSION:These data demonstrate that both swine IL-3 and KL are needed for prolonged enhancement of swine progenitor chimerism under these conditions, and suggest that the species specificity of either one or both of these cytokines may represent an important barrier to prolonged engraftment of swine bone marrow in humans.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Emery DW,Holley K,Sachs DH

doi

10.1016/s0301-472x(99)00058-2

keywords:

subject

Has Abstract

pub_date

1999-08-01 00:00:00

pages

1330-7

issue

8

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(99)00058-2

journal_volume

27

pub_type

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