Transcript What is the Most Likely Candidate for Successful Human Stem Cell

What is the Most Likely
Candidate for Successful
Human Stem Cell Therapy
Soonest?
• Blood
• Muscle
• Skin
• Why?
• How to select a
candidate?
Are SATELLITE CELLS the same
as MYOBLASTS?
Stem Cells: Mouse Embryonic
Stem Cells
http://www.youtube.com/watch?v=
5_9WNwC-4L8&feature=related
A muscle cell is a MYOFIBER
A myofiber is a SYNCYTIUM
What is a SYNCYTIUM?
How a
muscle
works –
structure
the
sarcomere
Making a Syncytium
Time-lapse Microscopy
showing Myoblast Fusion Into
Myotubes [Folch lab]
http://www.youtube.com/watch?v=
cQ-ahxaG8o4
Myoblasts Fusing into a Myotube
Beating Human Heart Cells
from Embryonic Stem Cells
http://www.youtube.com/watch?v=
JjVUYChg1M8&feature=related
Cycling Cells in the Life of a Muscle
Myotube with Satelite Cells
Satellite Cells in Muscle Repair
Muscle repair and growth – how
are they similar and different?
Effect of Ageing on Myoblasts
Myoblast transfer as a platform
technology of gene therapy
Peter Law, Tena Goodwin, Qiuwen Fang,
George Vastagh, Terry Jordan, Tunja Jackson,
Susan Kenny, Vijaya Duggirala, Charles
Larkin, Nancy Chase, William Phillips, Glenn
Williams, Michael Neel, Tim Krahn, and Randall
Holcomb
Gene Ther Mol Biol Vol 1, 345-363. March, 1998.
Becker dystrophy
normal
Becker dystrophy
Effect of transplanting 50 billion normal
myoblasts on enzyme leakage
First muscular dystrophy subject ever to
walk after wheelchair bound for years.
Muscle transplantation between young and
old rats: age of host determines recovery
• B. M. Carlson and J. A. Faulkner
• Am J Physiol Cell Physiol 256: C1262-C1266, 1989
• As compared with age-matched controls, extensor digitorum
longus (EDL) muscles autografted in young rats regenerated
significantly greater mass (1.8 times) and developed greater
maximum contractile force (2.6 times) than EDL muscles
autografted in old rats. A cross-age transplantation study
showed that the mass and maximum force of old muscles
grafted into young hosts were not significantly different from
those of young muscles grafted into the same young hosts.
Conversely, young muscle grafted into old hosts regenerated
no better than old muscles grafted into the same old hosts. We
conclude 1) that chronological age alone is not a factor that
limits the intrinsic ability of a muscle to regenerate and 2) that
the poor regeneration of muscles in old animals is a function of
the environment for regeneration provided by the old host.
Recombinant DNA
Technology
http://www.medicalive.net/243_rec
ombinant_dna
CAUTION!!!!!
…some links are fraught with errors
http://www.youtube.com/watch?v=YdjvUv-1vCI
Green Fluorescent Protein
http://gfp.conncoll.edu/
Techniques behind the study
• Grafting cells from green axolotl embryos to normal
animals before amputation, the researchers could track
the GFP to examine the fate of specific cell types in a
regenerating limb after amputation in juveniles.
• Using these techniques, the researchers looked at four
different tissue types: dermis, cartilage, muscle, and
Schwann cells - neural tissue that insulates the nerves of
the limbs. With the exception of dermal cells, they found
that the grafted green cells showed up only in those
same tissue types in the regrown limb.
Axolotl limb regeneration
Regenerated limb labeled
with GFP-actin in the
Schwann cells
axolotl