The Hematopoietic Stem Cell Therapy for Exploration of Space

Seigo Ohi, PhDAssoc Prof and Molec Geneticist, Depts Biochem & Molec Biol, Genetics &

Hum Genet, Pediatrics & CH, and Center for Sickle Cell Disease, Col of Medicine and Grad School

Howard University and Hospital, Washington, DCSupported by: NASA Institute for Advanced Concepts/USRA

Interplanetary Space Exploration:A) Readiness for catastrophic disorders:

- Hematological and cardiac abnormalities- Immunodeficiency- Muscle loss- bone losses- Neurological disorders - Cancer

B) Countermeasures:- Hematopoietic stem cell therapy (HSCT)- Gene therapy- Others, e.g. drug therapy

C) Robotization: Robotic medicine, e.g. Robotic HSC injection machine

OUR AIMS ARE TO DEVELOP THE HEMATOPOIETIC STEM CELL THERAPY AND GENE

THERAPY FOR ASTRONAUTS TO COUNTERMEASURE

SEVERE/INVASIVE DISORDERS CAUSED BY SPACE ENVIRONMENTS.

HEMATOPOIETIC STEM CELL THERAPY (HSCT)

Multiple Differentiating Potential of Adult Stem Cells

Adapted from: Vogel G, Science 290:1674 (2000)

Possible Benefits of HSCT• Hematological disorders:

– Space anemia– Immunodeficiency

• Muscle and bone losses• Neurological disorders• Cancer Therapy:

– Bone marrow replacement therapy for blood-born cancer, e.g. leukemia

– High dose chemotherapy

HSCT TO MAINTAIN ASTRONAUTS’ HOMEOSTASIS

HSCT FOR HEMATOLOGICAL

DISORDERS

The β-Thalassemic Mouse

WT β-THAL

HSCT FOR MUSCLE LOSS

The mouse model of hindlimb suspension unloading model

Multiple Differentiating Potential of Adult Stem Cells

Adapted from: Vogel G, Science 290:1674 (2000)

THE PROTOCOL

• Genetically mark HSCs with β-galactosidasegene: Transfection or use of Tg-mice.

• For β-gal Tg-mice: Isolate and expand HSCs; Strain 129S.

• Transplant the HSCs to 129S hindlimb-suspended mouse: Injection into the right leg.

• Isolate tissues from the recipient and stain by X-gal.

• Examine leg tissues for the blue stain.• Fine structural analysis of muscles.

GENETIC MARKING OF HSCs

A. Transfection B. Transgenic mouse

X-gal Staining of Normal- and β-gal-mouse Tissues

A. B. C. D. E. F.Intstn. Kdny. Liver Spln. Heart Lung

The mouse model of hindlimb suspension unloading model

Transplantation of β-gal HSCs to hindlimb-suspended mouse

Intestine Left leg Right leg

GENE THERAPY

PREVENTIVE MEDICINE based on human / robotic synergistic diagnosis and

minor operations:

Hematopoietic Stem Cell Therapy and Gene Therapy

ACKNOWLEDGEMENTS- Howard U.: J. Brezo, A.N. Roach, B.C. Kim

- NASA-NIH: W. Fitzgerald, L. Margolis, J. Zimmerberg

- Medical Col. of Wisconsin: D. Riley

Supported by: NASA Institute for Advanced Concepts/USRA

The End