Advances in stem cell technology
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WELCOME1
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Status of major diseases
(NIH, United States, 2013)2
Heart diseases
Diabetes Parkinson's Cancer AIDS Other0
10
20
30
40
50
60
70
80
Num
ber o
f pati
ents
(in
mill
ions
)
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Advances in stem cell technology
Manglam Arya2014-11-102
Centre for Plant Biotechnology and Molecular BiologyCollege of Horticulture
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Outline 1. Introduction to stem cells2. Types of stem cells 3. Types of human stem cells4. Induced pluripotent stem cells (iPSCs)5. Potential uses of iPSCs6. Success stories 7. Stem cell banking8. Plant stem cell technology and its application9. Summary 10. Conclusion
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Introduction to stem cells
Term given by William Sedgwick in 1886
Undifferentiated autologous cells
Self renewable capacity
Differentiated • Cells • Tissue • Organ
Show plasticity
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Types of stem cells Based on their ability
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Types of human stem cellsEmbryonic stem cells (ESCs) Adult stem cells (ASCs)
Strengths Pluripotent High replicative capacity
Weakness Immunological concerns Subjected to ethical debate
Strengths Multipotent and autologous Clinical safety
Weakness Limited number Limited replicative capacity
7(Diecke et al., 2014)
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Induced pluripotent stem cells (iPSCs)
Recently developed stem cells
Genetic modification of adult somatic
cells
Similar as embryonic stem cells
Differentiated into 3 germ layers
Noncontroversial
(Mariusz et al. 2014) 8
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Global publications on stem cells
(Servellen and Oba, 2014)9
2005 2006 2007 2008 2009 2010 2011 20120
200
400
600
800
1000
1200
Human embryonic stem cells (hESc) iPSCs
Year
Num
ber o
f pub
licati
ons
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Compound Annual Growth Rate(CAGR) for stem cells publication (2008-2012)
(Servellen and Oba, 2014)10
Human embryonic stem cells (hESc)
12%
iPSCs88%
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Potential uses of iPSCs
iPSCs Embryonic stem cells
Others- basic research and disease modeling
(Servellen and Oba, 2014)
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Regenerative medicine
"Process of replacing, engineering or regenerating human cells,
tissues or organs to restore or establish normal function”
– iPSCs are mostly used
– Tissues and organs grown in the laboratory
– Solves the problem of organ shortage
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(Diecke et al., 2014)
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…regenerative medicine
Regenerative medicine
Cardiac disease
Diabetes
Lung disease
Parkinson’sLiver disease
Spinal cord injury
Cancer
13(Ramachandran and Yellededahalli, 2011)
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Treatment of type -1 diabetes (T-1D)
• Uses human iPSCs
• Treated with activin A
• Develops insulin producing cells (IPC)
• All cells expressed Pdx-1 genes
• Injected into mouse kidney capsules
(Kim et al., 2015)
iPSCs colony Definitive endodermal
Pancreaticendodermal
Pro-endocrine progenitors
Pre-insulin producing cells
Insulin producing cells
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Result
Control has 400–500 mg/dl blood glucose
IPC transplanted <200 mg/dl in 3-6 mice
iPSCs are novel option for the treatment of T-1D
Bloo
d gl
ucos
e (m
g/dl
)
Time (minutes)
Control
IPC- transplanted
Glucose clearance
(Kim et al., 2015)15
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Treatment for AIDS
(Holt et al., 2010)
AIDS virus relies on a protein CCR5 (C-C chemokine receptor-5)
Hematopoitic stem/ progenitor cells (HSPCs)
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…treatment for AIDS
(Holt et al., 2010)17
Thymus Lung Spleen Bone marrow0
200400600800
100012001400160018002000
Hum
an C
D4+
T- ce
lls (n
o. o
f ce
lls p
er 5
000)
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Other developed regenerative medicineTissue or organ
developed Stem
cells usedUses Reference
Liver iPSCs Acute liver failure Chen et al., 2015
Kidney organoid iPSCs Nephrotoxicity screening, disease modeling
Takasato et al., 2015
Dopamine neuron ESC Parkinson’s disease Kriks et al., 2014
Cerebral organoid (model human brain)
iPSCs Disease modeling and treatment of brain diseases
Lancaster et al., 2013
Neurons iPSCs Neural disorder Corti et al., 2012
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iPSCs derived functional liver Cerebral organoid
Kidney organoid iPSCs derived neurons19
…other developed regenerative medicine
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Stem cells based gene therapy
• Genetic engineering technology for treatment of human
diseases dates to 1989
• Gene therapy has side effects
• iPSCs - new upgraded cellular vehicle or vector
• Homing effect
(Kim et al., 2014)
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Delivering of therapeutic transgenes
(Kim et al., 2014) 21
iPSCs
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Drug screening and development
• iPSCs technology revolutionizing medical science
(Jered et al.,
2014)
• Mechanisms and novel therapeutic molecular targets
• Opportunities for drug discovery
• Large chemical libraries to a list of candidate compounds
(Inoue and Yamanaka, 2011)
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…drug screening and development
(Faye et al., 2014) 23
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Success stories
• Red blood cells created from iPSCs
• In Britain- multimillion pound project
(Hough, 2010)
• American company City of Hope
• FAD approval for human trial for Treatment of HIV and diabetes
(Nicole and White, 2015)
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• Use of viral vector for gene delivery
• Genetic abnormality in the cells
• Formation of tumor-tumorigenesis
• Very low efficiency of reprogramming
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Disadvantage of iPSCs
(Nagvenkar and Sriraman, 2013)
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Stem cell research institutes in India
Name of institute Place
Centre for Stem Cell Science (CSCS) Hyderabad
International Centre for Stem Cell, Cancer and Biotechnology (ICSCCB) Pune
National Centre for Cell Science (NCCS) Pune
Institute for Stem Cell Biology and Regenerative Medicine (inStem) Bengaluru
Centre for Cellular & Molecular Biology (CCMB) Hyderabad
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Stem cell banking
• Stores stem cells at very low
temperature
• Regenerative medicine- develops
bioeconomy
• Destined as pillar of the bioeconomy
(Diecke et al., 2014)
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Steps in cord blood banking
Umbillical cord cut Cord blood collected Test are conducted for maximum safety
Processed to yield maximum stem cells
Stored in liquid nitrogen
(Knoppers and Isasi, 2010)
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Stem cell regulation in India
• Guidelines prepared by DBT and ICMR
• Conduct clinical trials
• License issued by Indian Institute of Science, Bengaluru
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(Jayaraman, 2014)
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Plant stem cell technology
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Plant stem cells
• Totipotent in nature
• Located in growing apices
• Grouped into niches- meristem
• WUS(WUSCHEL) gene- signal for proliferation
• CLV3(CLAVATA3) gene controls the expression of WUS gene
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….plant stem cells
Stem cells niches
WUS protein
Quiescent center
Stem cells in apical meristem Stem cells in root meristem
(Sablowski, 2010)32
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Applications
• Tissue culture
• Protect the endangered species
Plant stem cells extract
– Longevity of skin stem cells
– Promote skin’s ability to regenerate
– Delay biological ageing
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• Uttwiler Spatlauber
• Stem cells taken from fruit
• Extract obtained after lysis of cells
• Incorporated with lecithin liposomes
Apple stem cells as anti-ageing ingredient
(Schmid et al., 2008)
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Fruit of Uttwiler Spatlauber
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Control 0.01 0.102468
101214
Effect of Uttwiler Spatlauber stem cells extract on viability of umbilical cord stem cells
Concentration (in per cent)
cell
num
ber (
in la
khs)
Protection of human stem cells Extract of stem cells was tested for cell viability
(Schmid et al., 2008)35
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Control 0.01 0.10
102030405060708090
100
Uttwiler Spatlauber stem cells extract protects umbilical blood stem cells from UV- light
Concentration (in per cent)
Decr
ease
in c
ell n
umbe
r (in
per
cent
)…protection of human stem cells
(Schmid et al., 2008)
Effect of stem cells extract on UV-light treated cells
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Reversion of senescence signs in fibroblast cells
Gene After H2O2 treatmentcontrol
(% to untreated)
After H2O2+ 2% stem cell extract
(% to untreated)Cyclin B1 (induces proliferation)
73 130
Cyclin E1(controls cells cycle)
78 135
Insulin like growth factor II ( cells proliferation enhancer)
71 117
P53 (tumor suppressor gene)
63 137
Heme oxigenase 1 ( antioxident enzyme)
89 211
(Schmid et al., 2008)37
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Plant stem cells product in market
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Origin Trade name Source
Panax ginseng ActostemR Wkgbase ACT, Korea
Cyperus papyrus Crodarom Papyrus Crodarom, France
Centella asiatica Centella asiatica Stems GTMIRB, Italy
Rhododendron sp. Phyto cellsTectTM Alp RoseMibelle Biochemistry, Switzerland
Malus domestica Phyto cellsTecTM Malus
Vitis vinifera Phyto cellsTecTM Solar Vitis
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Summary
• Stem cells and its types
• iPSCs – newly developed stem cells
• Development of iPSCs and application in regenerative medicine
• Stem cell banking and its benefits
• Plant stem cell technology in cosmetics
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Conclusion
• Enormous opportunities for clinical applications
• Biological, ethical and financial challenges
• Unblocks the potential of iPSCs
• Common medicine for future
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THANK YOU
42
STEM CELLS CAN CREATE MIRACLES…
GIVE HOPE TO THE HOPELESS…
&
COULD MAKE LIFE IMMORTAL!!!