Induced pluripotent stem cells

INDUCED PLURIPOTENT STEM CELLS Presented by: VIDUR BHATIA M. Sc. (F), KUK.

Contents ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

Introduction ,[object Object],[object Object],[object Object]

History ,[object Object],[object Object],[object Object],[object Object],[object Object]

Conti….. ,[object Object],[object Object],[object Object]

Embryonic Stem cells Totipotent Pluripotent Multipotent Unipotent

Reprogramming of somatic cells to ES cells Somatic cell nuclear transfer Cell fusion Treatment with the extract of the pluripotent stem cells Stable expression of defined factors ( Cowan et al.,2005) ( Wilmut et al.,1997) (Takahashi and Yamanaka, 2006.)

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Stable expression of defined factors Twenty four candidate genes play pivotal roles in the maintenance of ES cell identity base on their hypothesis. (Takahashi and Yamanaka,2006.) Myb, Kit, Gdf3, Esrrb 21 22 23 24 Ecat1 Dppa5(Esg1) Fbox15 Nanog Eras Dnmt31 Ecat8 Gdf3 Sox15 Dppa4 Dppa2 Fthl17 Sall4 Oct3/4 Sox2 Rex1 Utf1 Tcl1 Dppa3 Klf4 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Symbol No.

[object Object],[object Object],[object Object],[object Object],(Takahashi and Yamanaka, August 25, 2006.)

[object Object],[object Object],WHAT ARE iPSCs ?

Genes responsible for pluripotency ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],(Takahashi and Yamanaka, 2006.)

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[object Object],Klf4 repress p53 directly p53 protein suppress Nanog during ES cell differentiation Klf4 contributes to activation of Nanog and other ES cell-specific genes (Rowland et al ., 2005; Lin et al ., 2004) Klf4 acts as an inhibitor of c-Myc-induced apoptosis through the repression of p53 (Zindy et al ., 1998) Klf4 activates p21CIP1, thereby suppressing cell proliferation .This antiproliferation function of Klf4 inhibited by c-Myc, which suppresses the expression of p21CIP1 ( Zhang et al ., 2000; Seoane et al ., 2002 )

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Production of iPSCs ,[object Object],[object Object],[object Object]

(1)Isolate and culture donor cells. (2)Transfect stem cell-associated genes into the cells by viral vectors. (3)Harvest and culture the cells according to ES cell culture, (4)A small subset of the transfected cells become iPS cells and generate ES-like colonies.

First generation ,[object Object],[object Object],[object Object],[object Object]

Limitations:- ,[object Object]

Second generation in mice ,[object Object],[object Object],[object Object]

Limitations:- ,[object Object],[object Object]

Human induced pluripotent stem cells ,[object Object],[object Object]

Pluripotency induction is a slow and gradual process ,[object Object],[object Object],[object Object],(Alexender Meissner et al.;2007)

Complications ,[object Object],[object Object],[object Object]

Identity ,[object Object],[object Object],[object Object],[object Object],[object Object]

iPS Cells - the Wave of Future ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

[object Object],[object Object],[object Object],iPS can be used for treatment of Parkinson’s disease

Mouse kidneys created using iPS cells A team of scientists has successfully used induced pluripotent stem (iPS) cells to create kidneys inside a mouse whose parents were genetically engineered so their offspring would not be born with the organ. (Hiromitsu Nakuchi; Mar. 10, 2009))

[object Object],[object Object],iPSc can be used to create Electrically Active Neuron (Michael Scott on February - 25 – 2009)

Somatic cells can be used to generate the β -cells ,[object Object],[object Object],(Qiao Zhou et al .,2008)

Conclusion ,[object Object],[object Object]

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Induced pluripotent stem cells

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Induced pluripotent stem cells