Download Chimeras

Interstate Alliance on Stem Cell Research
Chimeras
John Gearhart
James W Effron University Professor
Professor of Medicine and Veterinary Medicine
Director, Institute for Regenerative Medicine
University of Pennsylvania
September 10, 2008
University of Maryland Biotechnology Institute
Baltimore, MD
Definitions (as relates to mammals)
Mosaic: The occurrence in an animal of two or more
cell populations of different chromosomal
constitutions or chromosomal function developed
from a single zygote or conceptus
Chimera: an animal that is composed of cells derived
from two or more conceptuses
Hybrid: an offspring of parents from different
species through ‘crossbreeding’
Clone: an animal derived from a single individual
Transgenic: an organism whose genome has been altered
by the transfer of gene sequences from
another species
Human Chimera Prohibition Act of 2005
(Introduced in Senate)
109th CONGRESS
1st Session
S. 1373
To amend title 18, United States Code, to prohibit human chimeras.
IN THE SENATE OF THE UNITED STATES, July 11, 2005
Mr. BROWNBACK introduced the following bill; which was read twice and
referred to the Committee on the Judiciary
July 6, 1996 – February 14, 2003
ARCH DERMATOL/VOL 144 (NO. 3), MAR 2008
Microchimerism
1st introduced in the 70’s to describe
long term donor cell survival in a small
proportion relative to the host cells
following bone marrow grafts in mice
Sources:
blood transfusions (and bmt’s)
twinning (and loss of twin)
organ transplants
bidirectional trafficking during
pregnancy
Fetal origin of cells in maternal tissues
Fetal cells are transferred to the maternal
circulation during all human pregnancies
Persisting cells are found in a wide range of
tissues
Fetal cells persist in maternal blood and tissue
decades after pregnancy
Fetal cells with stem cell-like properties are
transferred: Pregnancy-associated progenitor
cells (PAPCs)
What are the consequences of fetal cells
in maternal tissues following pregnancy?
Hypotheses:
Bad microchimerism
Autoimmunity
Good microchimerism
Rejuvenation/repair
Associations between fetal cell microchimerism
and maternal autoimmune disease
Systemic sclerosis: blood and affected tissues
Significantly increased
Polymorphic eruption of pregnancy: skin
Significantly increased
Systemic lupus erythematosus: many tissues
Variable
Hashimoto’s disease: thyroid
Significantly increased
Primary Chimeras
Secondary Chimeras
(Secondary) Human Chimeras
Anyone who has received a blood
transfusion, a bone marrow transplant,
a pig heart valve, an organ transplant
Future: non-autologous stem cellderived therapies
Animal/Human Chimeras
(aka part-human animals or manimals)
Any animal receiving human
cells, tissues or organs
‘Humanized’ animals (genes as well)
Animals with human immune
system, organs (including brain?!)
Stem cells and chimeras
How much will the transplanted cells
contribute to an animals body or organ
functions?
Focus on two issues:
Germ cells
Brain
Factors to be considered with the
possible ‘humanizing’ of the brain
of chimeras
Stage of development when the cells
are introduced
The proportion/number of human cells
introduced
Site of graft
Relatedness of host to the human
Why do we want to make
animal/human chimeras?
In stem cell research, human cells are
the therapy. The fate and function
of these cells must be assessed in vivo
to determine their efficacy and safety.
Must also appreciate that this paradigm
is not w/o inherent concerns.
The FDA requires animal testing before
they are tested in humans.
Opposing views and concerns with
humanizing animals
Animal welfare issues
Respecting the boundaries of species
Respecting human ‘dignity’
Regulations and Oversight with
Stem Cells and Chimeras
Medical Research Council of Canada
Select Committee on Science and Technology,
UK Parliament
National Academy of Sciences Recommendations
US