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An attempt to complete the cerebral growth by mobilizing neural stem cells
Masayuki Okumura, Rafael B. Ribeiro, Nagib Curi, Carlos. E. P. Corbett and J.J. Gama-Rodrigues
Faculdade de Medicina da Universidade de S. Paulo - Brazil
[email protected]
Research in the field of Embryonic trunk or stem cells is still a babbel of scientific language. Modern scientists using various experimental models
could not reach a consensus.
Since 1998 when we used a protozoan (Trypanosoma cruzi, Chagas 1909) as a biological marker, we now understand the whole evolutionary
mechanism of the Embryonic trunk or stem cells from its primordial stage alI the way up to forming a new organ.
Injecting parasite into mice we were able to follow-up: a) its beginning with the formation of cytokine; b) production of primitive substance (primitive
amorphous mass - similar oocyte); c) penetration of T.cruzi into the gel: d) originating the embryonic trunk or stem cell; e) its three types of shape and
evolution (oval-nest: ring-unwinding and sphere-elongation), confirming its multipotentiality and f) up to the development of the definitive and diseased
organ ("chagasic megas", megacolon and others).
AAAS ANNUAL MEETING - WASHINGTON, DC. (17 – 21 FEBRUARY 2005)
Masayuki Okumura.; Rafael B.Ribeiro.; Nelson Tsuno*.; Nagib Curi and Joaquim Gama Rodrigues
Faculdade de Medicina Universidade de S. Paulo (Brazil) and Tokyo University (Japan)*
Remember: Right is always the laboratory animal; it is irrational and does not know the “ blindman and elephant” tale.
INTRODUCTION
Currently scientists are impressed with the versatility,
potentiality and pathway of “trunk or stem cells”, but
questions still remain unanswered1.2.
BACKGROUND
Some researchers are working towards clinical applications
with surprise and promising results, about the bone marrow
transplantation and blood from umbilical cords and the
founding of the umbilical cord banks.
RESULTS
and
DISCUSSION
Due to the lack of cells, the scientists estimate a ratio of “only one in 100,000 bone marrow cells may be trunk cells or embryonic stem
cells8”, or admit the cellular dedifferentiation or plasticity9. We wish to help clarify by a hypothesis: those cells do not exist freely in nature,
because they are formed after being stimulated and can be found in any tissue, as a Primitive amorphous mass, both in embryos and in
adult animals.
We demonstrate their presence (T.cruzi) in three different situations and evolutions6.7:
a) in tissues: tripomastigote (flagellate) transforming
into amastigote (oval), reproduce by successive
binary division and forms parasites nest.
1
3
2
Blood stream two adults: Trypanosoma cruzi.
Colon, Auerbach plexus: integral neuron with parasites
without inflammatory reaction (histology- HE. 400X)
Macrophage filled with amastigotes
b) in hematopoietic organs: embryonic liver (spherical cell) transformed
by an “elongation or direct mechanism” into epimastigote (tadpole)
4
Colon, Auerbach plexus rupture of nest within parasitic neuron
and ruptured of host cell without inflammatory reaction
c) in bone marrow and spleen (ring shaped amastigote) evolve by an
“uncoiling, unwinding or indirect mechanism” into epimastigote (tadpole)
OBJECTIVE
We can assume that there is “the Primitive Amorphous
Mass3”, which is formed before it eventually turns into the
embryonic stem cells or trunk cells whith we find throughout
the organism in a prevailing number in hematopoietic and
lymphopoietic organs.
METHODOLOGY
Inoculation of Trypanosoma cruzi4 into mice (abdomen way)
from the very first day through the 365th day under normal
control. We mated the diseased mice and we sacrificed
them weekly during pregnancy so that we could follow up on
the evolution of the unborn offspring.
The Tripanosomiasis americana (Chagas´ disease)5 is an
ideal disease for this study, because T.cruzi, functioning as
biological markers to study the “primitive amorphous mass”.
5
6
Liver, histology: slide with free
parasites in the capillaries and
sinusoids (Giemsa. – photo Kodak Film)
Liver, imprint: spherical and
developing forms resulting for
elongation (Giemsa. – photo Kodak Film)
Liver, imprint: Evolutionary form resulting
from elongation – resembling tadpole.
Sternal bone marrow, imprint: ring – shaped and
evolutive forms resulting from unwinding.
Sternal bone marrow: amastigote nest (histology, 400 X. H.E.)
(Giemsa – photo Kodak film)
11
Mouse: uterus bicorni
2nd
week with embryos and fetus
10
9
(Giemsa. – photo Kodak Film)
d) Examining liver, bone marrow and spleen
imprints of fetal and adult mice, we found greater
amount of “Primitive Amorphous Mass” in chagasic
embryos and fetuses (in 1st, 2nd and 3rd weeks of
pregnancy) and none in animals controls.
12
Mouse: uterus bicorni, with three weeks old fetus;
(Giemsa. - photo Kodak Film)
13
Fetal mouse “primitive
amorphous mass”
Bone marrow, imprint: parasite evolved by an
“unwinding or indirect mechanism”
14
Newborn and pregnant adults
15
Adult mouse: “primitive
amorphous mass”
The umbilical blood cord, rich in embryonic trunk or stem cells originates chiefly in the liver and in lesser amount in
bone marrow, spleen and also in other tissues where our “Primitive Amorphous Mass” (cellular matrix) is located.
CONCLUSION
REFERENCES
8
7
1.
2.
3.
4.
HELMUTH, L.- Stem Cells Hear Call of Injured Tissue Science, 2000, 290; 1479-1481.
VOGEL, G.- Stem Cells: New Excitement, Persistent questions Science, 2000, 290: 1672-1674.
OKUMURA, M. & GAMA-RODRIGUES, J.- Fruitful Jelly or Amorphous Primitive Mass Non published
CHAGAS, C.- Nova Tripanosomiase humana. Estudo sobre a morfologia e o ciclo evolutivo do Schizotrypanum cruzi, n.gen, n.sp, agente etiológico
de nova entidade mórbida do homem. Mem. Inst. Oswaldo Cruz, 1909, 2: 1-62.
5. CHAGAS, C.- Processos patogênicos da tripanosomiase americana. Mem. Inst. Oswaldo Cruz, 1916, 8: 7-36.
6. OKUMURA, M.- Primitive Amorphous Mass Non published
7. RIBEIRO, R.B.; et al. – Relato sobre a infecção crônica do Trypanosoma cruzi (cepa Y) em camundongos Swiss. Rev.
Brás. Medicina. Tropical, 1999, 32;334 (sup.1)
8. KRAUSE, D.S.- Multi organs, multi lineage engraftment by a single bone marrow derived stem cells. Cell, 2001, 105:
369-377
9. HOLDEN, C & VOGEL, G.- Plasticity: time for a reappraisal ? Science, 2002, 296: 2126-2129.
a) Pre-labor
b) Post childbirth
P.L.A.S. 25 year old lady in her 16th week of pregnancy while submitted to ultrasonography to determine
the sex was found to be carrying an anencephalic being.
On her 31st week, decided not to interrupt her pregnancy she asked us what to do as she knows of a
similar case that had a favorable outcome (MARCELA DE JESUS from Patrocinio Paulista taken care by
Dr. Marcia Beani Barcellos) being now six months of age and gaining weight like a normal child.
Similar to the treatment of Marcela de Jesus we suggested to the mother to take gama aminobutiric acid,
vitamins B1 and B12 pills plus fish broth which is rich in sphingomyelin.
Our objective (based on our experience at the University of São Paulo Medical School where we used
Trypanosoma cruzi of Chagas disease as a biologic marker and studied the origin, development and
destiny of the stem cells in animals) was to substitute the genetic code of the Trypanosoma by the
chemical radicals of GABA and sphingomyelin.
These substances swallowed by mouth are absorbed by the intestine and then through the portal
circulation reach the hepatic sinusoids; in contact with the primitive amorphous mass or cellular matrix
they form the hepatic neural stem cells.
A portion of blood containing cytokines and also rich in maternal stem cells enters the umbilical circulation
and reach the placenta then activating the fetal liver to produce the autochthonous hepatic stem cells.
Therefore the fetal blood is enriched by the materno-fetal neural stem cells.
The other maternal blood reaches the heart through the suprahepatic vein and the inferior vena cava.
Through the general circulation it reaches the bone marrow and spleen where the neural stem cells are
produced. As the neurons of the gray layer of the brain contain aminobutiric acid and the white layer
myelin rich in sphingomyelin we expect that both marking hepatic and bone marrow stem cells once
activated by their respective cytokine will be deposited in the central nervous system thus forming the
cortex and completing the formation of the brain.
Besides the medication we suggested that the obstetrician evaluate fetal conditions, having a CT scan or
MRI. We also suggested cesarean section because being incomplete the head without a skullcap and
eventual palatine fissure could suffer deformity during birth and head damage. The presence of a
neonatologist ready for possible reanimation and care of the newborn is important.
HISTORY: CGF, 46 years old, domestic servant, pregnant of 4 months, in the prenatal at an
ultrasonography, was diagnosed the presence of a fetus with anencephaly. She was religious and
decided maintain the gestation until the end.
On November 20th, 2006, a female child (Marcela de Jesus) born with 47cm and 2.5kg of weight, showing
cranium deformity, partial palate fissure, eyeball prominent, with anomaly in the lachrymal gland and
meningial hernia through the incomplete fontanel.
The computadorized tomography has been revealed aplastic cranium, with alteration in cranium basis,
palatine fissure, eyeball prominent and presence of cerebral stem.
The doctor Márcia Beani Barcellos attended the baby since the birth and adopted the following conduct:
1 - Lacteal alimentation;
2 – Eyeball lubrification with collyrium and
3 - Respiratory support with intermittent oxygenation
On 50th day of life, an associated teacher from Medicine Scholl of São Paulo University has been
suggested to doctor Márcia Beani Barcellos the attempt using no invasive cell therapy with nervous stem
cells for induce cortex formation, completing the brain, introducing by gastric sounding lead: the butyric
acid amine gamma with the lacteal diet.
By occasion of diet change, from lacteal to salt, add and ingest fish broth, which is rich in sphingomielyn.
Both substances, to the cross by liver produce the nervous stem cells hepatics and later, by general
circulation reach the hematopoietic organs, the bone marrow and spleen, creating the nervous stem cells
medullar.
Both stem cells (medullar and hepatics) containing the respective substances (butyric acid amine gamma
and sphingomielyn) with cytokine orientation, adhere at cerebral stem, forming the gray and white layers
of cortex and complete the central nervous system, the brain.
The child has discharge from hospital at 5 month after the birth; she is at the moment in residence,
continuing under medical careful at distance.