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STEM CELLS AND REGENARATIVE MEDICINE
O.L. Kukharchuk, V.V. Radchenko,
A.B. Padma Priya, A.O. Kukharchuk
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]
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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
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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
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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.
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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
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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)
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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
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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
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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
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FETAL PROGENITOR CELLS TRANSPLANTATION
Bright example of fetal progenitor cells induced reparative regeneration is polytrauma.
In these conditions, likewise after any complicated operation, body of patient mobilizes all stem cells resources to restore the function of the damaged organs and tissues.
If stem resources is insufficient then the patient dies.
Regenerative medicine contributes chance of survival in such type of patients.
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FETAL PROGENITOR CELLS IN BURNS III-A STAGE TREATMENT
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]
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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
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]
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TRANSPLANTATION OF FETAL PROGENITOR CELLS IN POSTOPERATIVE PERIOD TO PANCREONECROSIS PATIENTS
Removal of cord tissue implant following 3 days after operation
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]
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TRANSPLANTATION OF FETAL PROGENITOR CELLS IN POSTOPERATIVE PERIOD TO PANCREONECROSIS PATIENTS
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
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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)
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CHRONIC LEGS ISCHEMIA• Type of cells
suspension: hematopoietic cells of fetal liver.
• Gestation term: 12 weeks.
• Dose: 35,0 x 10^6/ml. • Phenotype: CD34^+
CD133^+ CD38^- CD45RA^low CD71^low CD7HLA-DR^low.
• Amount of transplantation: 1
• Follow-up period: 16 months
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CHRONIC LEGS ISCHEMIA
Surgical treatment: local injection of Fetal progenitor cells along the sclerotic arteries
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CHRONIC LEGS ISCHEMIA: CASE REPORT
BEFORE CELL TRANSPLANTATION
AFTER CELL TRANSPLANTATION
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CHRONIC LEGS ISCHEMIA: CASE REPORT
BEFORE CELL TRANSPLANTATION
AFTER CELL TRANSPLANTATION
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Level of microcirculation (unit) Before treatment - 4.28 ±0.34 1 month after EPC–transplantation - 5.24±0.27 (р<0.05) 3 month after EPC–transplantation - 6.32±0.41 (р<0.05) 6 month after EPC–transplantation - 7.57±0.62 (р<0.01)Reserve of capillarity blood stream (%) Before treatment - 89.32±12.5 1 month after EPC–transplantation - 112.34±10.9 (р<0.01) 3 month after EPC–transplantation - 137.83±9.2 (р<0.05) 6 month after EPC–transplantation - 150.31±10.5 (р<0.05)Dilatation of precapillary sphincters Before treatment - ( - ) 1 month after EPC–transplantation - ( + ) 3 month after EPC–transplantation - ( + ) 6 month after EPC–transplantation - ( + )Distance of painless walk Before treatment – 50 m 1 month after EPC–transplantation - 300 m 3 month after EPC–transplantation - 450 m 6 month after EPC–transplantation - 500-1500 m
RESULTS OF ENTIRE CELL-TREATMENT GROUP
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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%
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LIVER CIRRHOTIC PATIENTS
In clinic 43 patients were examined with alcoholic liver cirrhosis:
• Age of patients: from 35 to 55 years.
• Disease span - 7,100,25 years.
• Patients had last stage of disease with higher level of liver injury (alternative treatment – liver transplantation)
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LIVER CIRRHOTIC PATIENTS
• Type of cells suspension: hematopoietic cells and hepatoblasts of fetal liver
• Gestation term: 6-8 weeks
• Dose: 15,0 x 10^6/ml. • Phenotype: CD34^+
CD45RA^low CD71^low CD7HLA-DR^low Albumine^+
• Amount of transplantation: 1
• Follow-up period: 14 months
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LIVER CIRRHOTIC PATIENTS
FPC- transplantati
on
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LIVER CIRRHOTIC PATIENTS
FPC- transplanta
tion
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PATIENTS ESTIMATION ON EFFICACY OF FETAL PROGENITOR CELLS RANSPLANTATION AT THE END OF
INVESTIGATION:
“SIGNIFICANT IMPROVEMENT” – 95%
“IMPROVEMENT” – 5%
“NON SIGNIFICANT IMPROVEMENT” – 0%
“WITHOUT CHANGE” – 0%
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DIABETES MELLITUS TYPE 2
• FPC-transplantation significantly decrease blood levels of glucose and Hb-Glu in patients with type 2 of diabetes mellitus
FPC- transplantati
on
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DIABETES MELLITUS TYPE 2
FPC-transplantation significantly decrease blood levels of insulin and C-peptide
FPC- transplantatio
n
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SEXUAL DYSFUNCTION
• Treatment: intravenous and subcutaneous human FPC administration.
• Type of human cells suspension: hematopoietic cells of fetal liver and progenitor cell, all type.
• Gestation term: 6-7 weeks. • Dose: 55,0 x 10^6/ml. • Phenotype: CD34^+ CD133^+
CD38^- CD45RA^low CD71^low CD7HLA-DR^low.
• Amount of transplantation: 1• Follow-up period: 26 months
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CHARACTERISTICS OF SEXUAL FUNCTION BEFORE FETAL PROGENITOR CELLS TRANSPLANTATION
Before start of tests
2 of 4 men have imperfect sexual function.
2 of them has climax. Two patient has subnormal libido, its absence – two other patient.
All 6 women has
climax with absence of libido
Patient Patient sexsex ageage ObservatiObservation time on time ((monthsmonths))
Sexual Sexual function function
Libido Libido
G1G1 manman 5858 1414 Not Not infringedinfringed
Subnormal Subnormal
G2G2 manman 6565 1212 Climax Climax Absent Absent
G3G3 manman 6161 1818 Not Not infringedinfringed
SubnormalSubnormal
G4G4 manman 6363 1515 ClimaxClimax AbsentAbsent
G5G5 womanwoman 5959 1818 ClimaxClimax SubnormalSubnormal
G6G6 womanwoman 6060 1414 ClimaxClimax AbsentAbsent
G7G7 womanwoman 5858 1212 ClimaxClimax AbsentAbsent
G8G8 womanwoman 6868 1616 ClimaxClimax AbsentAbsent
G9G9 womanwoman 6767 1616 ClimaxClimax AbsentAbsent
G10G10 womanwoman 6565 1717 ClimaxClimax AbsentAbsent
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CHARACTERISTICS OF SEXUAL FUNCTION AFTER FETAL PROGENITOR CELLS TRANSPLANTATION
Six months after transplantation the potency of all men was restored on a back of sharp rise of libido.
3 women have
restored menstrual cycle. Appearance of libido – all of them.
Patient Patient sexsex ageage Observation Observation time time ((monthsmonths))
Sexual function Sexual function Libido Libido
G1G1 manman 5858 1414 Not infringedNot infringed Elevation Elevation
G2G2 manman 6565 1212 Potency is Potency is renewed renewed
ElevationElevation
G3G3 manman 6161 1818 Not infringedNot infringed ElevationElevation
G4G4 manman 6363 1515 Potency is Potency is renewed renewed
ElevationElevation
G5G5 womanwoman 5959 1818 Appearance of Appearance of menstrual flux menstrual flux
ElevationElevation
G6G6 womanwoman 6060 1414 Without changesWithout changes Appearance Appearance
G7G7 womanwoman 5858 1212 Appearance of Appearance of menstrual fluxmenstrual flux
AppearanceAppearance
G8G8 womanwoman 6868 1616 Appearance of Appearance of menstrual fluxmenstrual flux
AppearanceAppearance
G9G9 womanwoman 6767 1616 Without changes Without changes
AppearanceAppearance
G10G10 womanwoman 6565 1717 Without changesWithout changes AppearanceAppearance
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THE CLINICAL EFFECTIVENESS OF THE FPC-TRANSPLANTATION AT DIFFERENT FORMS OF MALE INFERTILITY
We performed complex investigation of 29 infertile men; with secretory infertility – 19 patients; with excretory – 10 patients. The program of investigation included sperm's analysis and explanation of the sex hormones level in blood.
The control investigation were conducted over 3 month after the FPC-transplantation.
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THE CLINICAL EFFECTIVENESS OF THE FPC-TRANSPLANTATION IN SECRETORY FORM OF MALE INFERTILITY
Sperms volume, ml Before transplantation (n=19) - 3,73±0,50 After transplantation (n=19) - 3,93±0,38Concentration of spermatozoids (bill/ml) Before transplantation (n=19) - 4,81±0,96 After transplantation (n=19) - 11,32±1,43Amount of spermatozoids (bill) Before transplantation (n=19) - 14,89±0,82 After transplantation (n=19) - 43,89±4,82
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THE CLINICAL EFFECTIVENESS OF THE FPC-TRANSPLANTATION IN EXCRETORY FORM OF MALE INFERTILITYSperms volume, ml Before transplantation (n=10) - 3,86±0,17 After transplantation (n=10) - 4,30±0,11Concentration of
spermatozoids (bill/ml)
Before transplantation (n=10) - 49,75±4,03 After transplantation (n=10) - 53,62±5,26Amount of
spermatozoids (bill) Before transplantation (n=10) - 141,00±8,40 After transplantation (n=10) - 227,20±17,1
Motility of spermatozoids “a” (%)
Before transplantation (n=10) - 6,60±044 After transplantation (n=10) - 13,25±1,08Motility of
spermatozoids “b” (%) Before transplantation (n=10) - 11,67±1,03 After transplantation (n=10) - 16,75±1,19Motility of
spermatozoids “a + b” (%)
Before transplantation (n=10) - 17,17±1,42 After transplantation (n=10) - 30,00±1,75
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CONCLUSIONS
• We established the statistically true increasing of concentration and quantity of spermatozoids in secretory infertility (67%); and statistically true increasing of motility of spermatozoids in excretory infertility men (70%).
• After transplantation 40% treatments men had positive reproductive result.
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THANKS FOR YOUR ATTENTION !
More detailed information about the clinical application of fetal progenitor
cells mentioned in the information brochure