In Utero Stem Cell Transplantation

Key Points

In utero transplantation (IUT) has the potential to cure or ameliorate many disorders before birth.
Animal models for studying IUT have fundamental differences from human models in regard to immunologic ontogeny and placentation.
Naturally occurring events during pregnancy result in chimerism in large animals and in humans and support the concept of IUT.
Using mesenchymal stem cells for IUT may be possible in disorders with a functioning immune system.
Development of advanced medicinal therapy products for use in IUT is complicated and requires large resources and knowledge but holds great promise for the future.

Introduction

The first successful in utero transplantation (IUT) was reported by Touraine et al . in 1989. The report was followed by a limited number of IUTs in human fetuses with severe combined immune deficiency (SCID). Most of these reports claim partial engraftment of the transplants. Several researchers tried a similar approach with haematopoietic stem cell (HSC) transplantation in utero for nonimmunologic disorders; unequivocally, these cases failed. HSC is the stem cell that give rise to all blood cells, both of the myeloid and lymphoid lineages. The arguments for IUT, as summarised in Table 45.1 , are well known and have repeatedly been broadcasted in different reviews on this topic for almost 3 decades. However, we are still lacking knowledge on why IUT with HSC in fetuses with normal immunologic function do not engraft, and the evidence supporting the arguments are, to put it cautiously, not very strong.

TABLE 45.1

Arguments and Evidence for In Utero Transplantation (IUT) with Haematopoietic Stem Cells (HSCs) and Mesenchymal Stem Cells (MSCs) ^a

Arguments for IUT with stem cells	Evidence HSC	Evidence MSC
Right-to-left heart shunting that enhances systemic distribution of the cells
Small size of the fetus allows big dose
Treat before severe consequences of the disease
In fetal life, large-scale migration of stem cells takes place
Allows transplantation across HLA barriers
Donor-specific tolerance induction
Niches for exogenous stem cells
Psychological advantages
Less expensive than postnatal transplantation

HLA, Human leukocyte antigen.

a Green , some evidence; red, poor evidence. The darker shades depict less ( red ) and more ( green ) evidence.

A number of reviews on this topic have been published, with extensive examination of past literature on animal work and previous human experience. Recently two excellent reviews on IUT with HSC were published, and we will therefore in the present review focus mainly on IUT with mesenchymal stem cells (MSCs). MSCs are the stem cells that give rise to cell types of the mesodermal lineage, such as osteoblasts, chondrocytes, myocytes and adipocytes. Before embarking on such undertaking, we will briefly comment on the most current experience of IUT in animal models and whether we can learn more from nature regarding engraftment of foreign stem cells in human fetuses.

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