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STEM CELLS AND REGENARATIVE MEDICINEFETAL PROGENITOR CELLS

EmProCell Clinical Research Pvt. Ltd., Mumbai

SPEAKER:PROFESSOR

KUKHARCHUK OLEKSANDR

Currently in EmProCell cryobank we have fetal stem cells of the brain, spinal cord, heart, lungs, liver, kidneys, pancreas and adrenal, muscles and bones, skin and placenta. We are open for collaboration in the field of Regenerative Medicine. Contact us: [email protected], [email protected]

mailto:[email protected],[email protected]

TRANSPLNATATION OF STEM CELLS WITHOUT ITS PRELIMINARY

DIFFERENTIATION INTO SPECIALIZED TISSUE – IS PLAYING WITH RUSSIAN

ROULETTE

FETAL PROGENITOR CELLS ARE THE CELLS DERIVED FROM THE TISSUES OF ABORTUS FETUS

• The following types of cells can be derived from abortive material of different gestation terms (from 6 to 20 weeks):

• - liver progenitor cells• - neural progenitor cells• - gastric and intestinal

progenitor cells• - lung progenitor cells• - kidney progenitor cells• - skin progenitor cells• - bone tissue progenitor

cells• - pancreatic progenitor

cells

Fetal chondrocytes has high potential to

multiplication, they can be isolated in sufficient

quantity for transplantation or for obtaining specialized fetal growth factors

Fetal chondrocytes

FETAL PROGENITOR CELLS FROM HEART TISSUE

From fetal heart tissue have been isolated human fetal cardiomyocytes, cardiac human fibroblasts, adventitial fibroblasts, human microvascular endothelialcells, endothelial progenitor cells, mesenchymal stem cells, and vascular smooth muscle cells.Transplantation of these cells is effective for treatment of myocardial infarct and dilatation cardiomyopathy.

HAEMOPOIETIC PROGENITOR CELLS OF FETAL LIVER WITH PHENOTYPE CD133+

Progenitor hematopoietic cells of fetal liver capable to angio-myogeneic differentiation, stimulates blood cells formation and formation of new vessels, induces central immunological tolerance and enables regeneration of tissues practically all damaged organs

Ischemic muscle tissue: the area of myosymplast with

myoni

Three months after cells transplantation

HEMATOPOIETIC PROGENITOR CELLS OF FETAL LIVER WITH PHENOTYPE CD133+

Human CD133 fetal liver progenitor cells promote the healing of diabetic ischemic ulcers by paracrine stimulation of angiogenesis.Accelerated wound closure in the presence ofCD133 cells (A, middle) is associated with higher temporary wound capillarization at day 7 (B). Capillary density declines tolevels of wounds treated with CD133 cells or collagen gel alone by day 14 (C)

Tissue of fetal kidney consists all cellular elements in developmental stages, which has potential to replace damaged (injured) renal structures in adults.From 12-13 and till 18-20 weeks of human gestation: (a–b) localization of SIX2 to the MM, predominantly to the CM. (c–d) shaped bodies and renal stroma.(e–f) nephrogenic zone and newly forming tubules. (g–h) nephrogenic cortex, parietal epithelium of fetal glomeruli.(i–j) some differentiated tubules.

FETAL KIDNEY PROGENITOR CELLS

Neural fetal progenitor cells consists from precursors of primary neuroglia, dopaminergic neurons and oligodendrocytes, that lies on the grounds of therapeutical effects of the fetal neural cells transplantation in neurodegenerative diseases

FETAL NEURAL PROGENITOR CELLS

FETAL PANCREATIC PROGENITOR CELLS

Fetal pancreas consist cells – precursors of Langerhans islets cells, that could be the basis for treatment in diabetes mellitus 1 type

FETAL PROGENITOR CELLS IN BURNS III-A STAGE TREATMENT



TRANSPLANTATION OF FETAL PROGENITOR CELLS IN POSTOPERATIVE PERIOD TO PANCREONECROSIS PATIENTS

Sewing of umbilical cord

Ready implant

Insertion of implant on the zone of pancreatic necrosis

De-freezing umbilical cord




Removal of cord tissue implant following 3 days after operation




Fetal progenitor cells

Introduction of fetal progenitor cells stem cells in the subclavian

veinCurrently in EmProCell cryobank we have fetal stem cells of the brain, spinal cord, heart, lungs, liver, kidneys, pancreas and adrenal, muscles and bones, skin and placenta. We are open for collaboration in the field of Regenerative Medicine. Contact us: [email protected], [email protected]

Mortality rate reduced to 9 times. In course of 3 years after treatment formation of cysts in pancreas were not

observed


CHRONIC LEGS ISCHEMIA

In clinic 65 patients were examined with chronic legs ischemia. Age of patients: from 55 to 78 years. Patients had last stage of disease (alternative treatment – leg amputation)

CHRONIC LEGS ISCHEMIA

Surgical treatment: local injection of Fetal progenitor cells along the sclerotic arteries

CHRONIC LEGS ISCHEMIA: CASE REPORT

BEFORE CELL TRANSPLANTATION

AFTER CELL TRANSPLANTATION

CHRONIC LEGS ISCHEMIA: CASE REPORT

BEFORE CELL TRANSPLANTATION

AFTER CELL TRANSPLANTATION

PATIENTS ESTIMATION ON EFFICACY OF FETAL PROGENITOR CELLS TRANSPLANTATION AT

THE END OF IVESTIGATION:“SIGNIFICANT IMPROVEMENT” – 90%

“IMPROVEMENT” – 10%“NON SIGNIFICANT IMPROVEMENT” – 0%

“WITHOUT CHANGE” – 0%

Development program of progenitor cells is determined in formation of tissue cells of particular type – cardio, muscle, renal, lung and etc. This means that after isolation of such cells and introducing to patient progenitor cells will continue to differentiate exclusively in the predetermined cells of fetal liver – fetal hepatoblasts. These cells capable to produce only hepatocytes in future differentiation – liver cells, which and will restore damaged cirrhotic liver tissue of the patient.

Thus, in time of fetal organs formation, fetal cells lose stemness, and became progenitor cells.

So first advantage of fetal progenitor cells – they do not require additional manipulation, related with expansion and directed differentiation as such they can be easily isolated in large amount and they are already restricted under formation of particular type of tissue. Fetal progenitor cells after separation ready for use without any additional manipulation and treatment with fetal progenitor cells – this is organ-specific treatmentю

As such fetal progenitor cells are preformed under formation of specialized tissue cells i.e. THEY ARE NOT STEM, they NEVER DEVELOP INTO CANCER CELLS.

Secondly and most significant advantage is fetal progenitor cells – they are biologically cannot be source of cancer cells as such they are not stem cells.

Unique property of fetal progenitor cells – their capability to penetrate through histo-hematic barrier inclusive through hemato-plancental barrier – in blood of mother.

They circulate in first trimester fetal blood and have been found to traffic into the maternal circulation, engrafting in bone marrow, where they remain microchimeric for decades after pregnancy. Using fetal progenitor cells in regenerative medicine offers the practical advantages of avoidance of immune rejection, increased engraftment, and treatment before disease pathology sets in.

Fact is in pregnant women blood presence of progenitor cells of her fetus known earlier and captured special attention. In nature nothing is coincidence and unuseful, all has its biological sense. In what is the biological sense appearance of child’s fetal progenitor cells in mother’s blood? Fact is that fetus according to its genetic is transplantat for mother – kind of foreign organ.

Fetal tissue by protein (antigens) content incompatible with immune system of the mother due to half of the protein gene codes received from father. Besides, there is peculiar kind of move towards perfection – cross exchange of genes between chromosomes of father and mother (crossing-over). If such exchange did not happen than born child would have exactly be half copy of parents – 50% of mother, and 50% of father.

As the result of crossing-over completely new protein-antigen characteristics of body arises. Therefore organ of children do not get engrafted to parents after transplantation.

So, fetus – foreign “organ” for mother. Subsequently, during pregnancy period rejection reaction of transplantant (graft) should start. But immune system of pregnant women does not react with the protein antigen of the child. Scientists have searched for the answer to this question in the peculiarities of the blood-placental barrier, which, according to some of them, do not allow the mother's antibodies in the blood of child. And how then to be with all known Rhesus conflict when antibodies Rh-negative mother lead to miscarriage with Rh-positive fetus?

Attempts to explain absence of rejection reaction of the fetus is that mothers T lymphocytes do not fall in blood of child or special cells in the placenta inactivate T cells aggressive to the embryo tissues that too seemed to be failed. Mothers T-lymphocytes are observed in the fetus and they are active. Moreover during pregnancy mothers immune system components protects fetus from infectious agents.

So why do fetus not rejected by the immune system of the mother? As the result of long-term scientific work of EmProCell staff was shown that these fetal progenitor cells joins the pregnant women’s blood inducing immune tolerance – condition in which child body accepted by mother’s body as its own “organ”.

This continues for 9 months, followed by a sudden change in mother’s hormonal levels that blocks immune tolerance to the fetus and birth occurs. Note that childbirth - a typical acute graft rejection when transplanted organ such as the kidney, is rejected together with surgical sutures junction from donor kidney vessels and vessels of the recipient. The joining place of child’s body and the mother – placenta. Particularly from the moment of placental abruption physiological childbirth begins.

Consequently, fetal progenitor cells have one more highly significant properties – they are capable of inducing immune tolerance to themselves! This means that after introduction of fetal stem cells to patient they do not reject by the patient’s immune system, they easily get engrafted and fulfils its function – replaces damaged disease tissue of the patient’s body.

THE NEW ENGLAND JOURNAL OF MEDICINE (1995), 332 (17), 1118-1124.

NEUROPATHOLOGICAL EVIDENCE OF GRAFT SURVIVAL AND STRIATAL REINNERVATION AFTER THE TRANSPLANTATION OF FETAL MESENCEPHALIC TISSUE IN A PATIENT WITH PARKINSON’S DISEASE

JEFFREY H. KORDOWER , THOMAS B. FREEMAN, BARRY J. SNOW, FRANÇOIS J.G. VINGERHOETS , ELLIOTT J. MUFSON, PAUL R. SANBERG, ROBERT A. HAUSER, DONALD A. SMITH, G. MICHAEL NAUERT, DANIEL P. PERL, C. WARREN OLANOW

Mov Disord. 1998 May;13(3):383-93.Fetal nigral grafts survive and mediate clinical

benefit in a patient with Parkinson's diseaseKordower JH, Freeman TB, Chen EY, Mufson EJ,

Sanberg PR, Hauser RA, Snow B, Olanow CW.

http://www.ncbi.nlm.nih.gov/pubmed/9613726

Fetal Progenitor Cells & Spinal Injury

USEFULNESS. By EmProCell organ-specific treatment technology – not less 70 units.

RISK. Progenitor cells are ready for use; no cancer transformation; no reaction of transplant rejection – 1 unit.

PRICE. From 5000 till 5000 USD – 1 unit. USEFULNESS / RISK / PRICE: 70 / 1 / 1 = 70 units. Remember, that maximum level of USEFULNESS /

RISK / PRICE = 100 units.

Fetal Progenitor Cells & Non-organ-specific & organ-specific autoimmune diseases



PRICE. From 5000 till 5000 USD – 1 unit. USEFULNESS / RISK / PRICE: 70 / 1 / 1 = 70 units. Remember, that maximum level of USEFULNESS / RISK /

PRICE = 100 units.

Fetal Progenitor Cells & Liver Cirrhosis




PRICE = 100 units.

Fetal Progenitor Cells & chronic leg ischemia and non-healing wounds / ulcers




PRICE = 100 units.

THANKS FOR YOUR ATTENTION !

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FSC and RM