The Hematopoietic Stem Cell Therapy for Exploration of Deep Space

Abstract

Astronauts experience severe/invasive disorders caused by space environments. These include hematological and cardiac abnormalities, bone and muscle losses, immunodeficiency, neurological disorders and cancer. Exploiting the extraordinary plasticity of hematopoietic stem cells (HSCs), which differentiate not only to all types of blood cells, but also to various tissues, including muscle, bone, skin, liver, and neuronal cells, we advanced a hypothesis that some of the space-caused disorders might be amenable to hematopoietic stem cell therapy (HSCT) so as to maintain astronauts' homeostasis. If this were achievable, the HSCT could promote human exploration of deep space. Using mouse models of human anemia (β-thalassemia) and spaceflight (hindlimb suspension unloading system), we have obtained feasibility results of HSCT for space anemia, muscle loss, and immunodeficiency. For example, the β-thalassemic mice were successfully transplanted with isologous HSCs, resulting in chimerism of hemoglobin species and alleviation of the hemoglobinopathy. In the case of HSCT for muscle loss, β-galactosidase-marked HSCs, which were prepared from βgalactosidase-transgenic mice, were detected by the X-gal wholemount staining procedure in the hindlimbs of unloaded mice following transplantation. Histochemical and physical analyses indicated structural contribution of HSCs to the muscle. To investigate HSCT for immunodeficiency, β-galactosidase-transformed Escherichia coli was used as the reporter bacteria, and infected to control and the hindlimb suspended mice. Results of the X-gal stained tissues indicated that the HSCT could help eliminate the E. coli infection. In an effort to facilitate the HSCT in space, growth of HSCs has been optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

Expansion of human hematopoietic stem cells for transplantation: trends and perspectives

“…Both systems were used to culture human embryonic stem cells (hESC), showing that STLV reduced the aggregation of hESC and they attained a 4-fold increase in productivity respect to the Petri dish cultures (Gerecht-Nir et al 2004). The NASA-RWV systems have been used to study the effects of microgravity on murine HSC and evaluating the hematopoietic homeostasis during long space expeditions (Ohi et al 2004). These RWV bioreactors could be tested for human HSC expansion for transplantation.…”

Hematopoietic stem cells from peripheral blood the perspective of non-mobilized peripheral blood

“…The high aspect ratio vessel (HARV) bioreactor has a similar design, but the rotating speed can be slower than STLV. The NASA RWV systems have been used to study the effects of microgravity on murine HSC and evaluating the hematopoietic homeostasis during long space expeditions [81].…”