The Hematopoietic Stem Cell Therapy for Exploration of Space Seigo Ohi, PhD Assoc 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, DC Supported 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-galactosidase gene: Transfection or use of Tg-mice. • For β-gal Tg-mice: Isolate and expand HSCs; Strain 129S. • Transplant the HSCs to 129S hindlimbsuspended 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-galmouse Tissues A. Intstn.
B.
C.
D.
E.
F.
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