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Scope and Application of Stem Cell Research in Livestock
Jayanti Tokas1, Puneet Tokas2, Shailini Jain3, Hariom Yadav3
1Department of Biotechnology, JMIT, Radaur, Haryana, India
2KITM, Kurukshetra, Haryana, India3NIDDK, National Institute of Health, Bethesda, MD 20892,
USAEmail: [email protected]
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Stem Cell
Stem cells are master cells with two important characteristics
Unspecialized cells capable of their own renewal Ability to differentiate into different cell types
The stem cells may have various differentiation potentials
Totipotent Pluripotent Multipotent Unipotent
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Types of stem cells
Embryonic stem cells
Adult stem cells
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Characteristics of Embryonic stem cells
Derived from ICM/epiblast of Blastocyst Pluripotent Long-term self-renewal Exibit and maintain a stable diploid normal
complement of chromosome Expression of Oct-4 Lacks G1 check point in the cells cycle Don’t show X inactivation
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Stemness Genes
Oct4 Nanog SSEA1 SSEA2 SSEA3 BMP4
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Characteristics of Adult stem cells
Long-term self-renewal Give rise to mature cells having characteristic
morphologies and specialized functions Rare Dispersed in tissues throughout the body Origin of adult stem cells in tissues is yet not
known
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Tissues containing adult stem cells
Bone marrow Skeletal muscle Epithelia of skin and digestive system Cornea retina Peripheral blood Spinal cord Blood vessels Testes Liver Pancreas Kidney Heart, etc
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Stem cells speciality Apoptosis
No apoptosis in stem cells
TelomereNo shortening of telomere in stem cells
DNA MethylationMinimum DNA methylation in stem cells
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ES cells from livestock species
Iwaski et al 1990 ICM proportion lower in bovine IVF embryos than in vivo produced
Saito et al 1992 Bovine embryonic stem cells grow slower than murine embryonic stem cells
Hamers et al 1995 Bovine culturing embryo derived cells resemble epithelial cells rather than pluripotent ICM cells
Talbot et al 2000 Bovine embryonic cells grew as cell sheets. Passaging by physical dissociation
Li et al 2003 Porcine ICMs isolated by enzymatic method. Two embryonic cell lines cultured upto 6 passages
van Eijk et al 1999 Bovine Oct 4 pseudogene isolated Wang et al 2005 ES cells from cloned bovine embryos with marker staining
pattern similar to bovine blastocystsYadav et al 2005 Bovine ICM derived cells express the Oct4 ortholog
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Major Applications
Animal model testing for pharmaceutical research Use of stem cells in transplantation and cell replacement
therapy Conservation of endangered species Understanding fundamental events in embryonic
development Therapeutic delivery system To resolve mysteries of developmental biology To investigate genes involved in differentiation and
development Cell banking for research applications
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Identification of stem cells
Cell morphology
Expression of unique cell surface antigens
Characterization of biochemical markers such as tissue
specific enzymatic activity
Expression of genes that are unique to a particular cell
type
Nuclear chromosomal karyotype to access genetic
stability
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Scope Pharmaceuticals: diabetes, cardiac anomalies,
neurodegeneration, and infertility Neutraceuticals : produce heterologous nutrients Understanding early embryonic development Model for in vitro drug and immunity screening Producing environment friendly animals eg. Phytase and
methane Tissue remodeling and engineering Cell-cell communication and differentiation Conservation Germ stem cells challenge age old dogma of female born with
fixed number of oocytes
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Livestock stem cells
Farm animals are contributing in human health through
Nutrition Producing biomedicine Cell therapy Xenotransplantation
With decoding of the genome sequences in animals, stem cell promise to resolve many mysteries of the developmental biology
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Transgenic animals with important agricultural traits
Bovine alpha lactalbumin in mammary glands of sows–improves lactation performance
Sheep carrying Kerartin – IGF-1 construct shows expression in skin for clear fleece in transgenic animals
Transgenic pig bearing an hMt-pGH construct tightly regulated by Zinc feeding - improves traits as growth rate, feed conversion, body fat muscle ratio
Phytase gene exclusively expressed in salivary gland enables the pigs to digest phytate which can be metabolized by the intestine. Release low phosphorus in manure
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Transgenic in Biomedicine
Proteins synthesized in farm animals milk
Bovine - 2 Human lactoferrin Caprine - 5 TPA Ovine - 4 Alpha AT Pigs - 2 AT III Rabbits - 7 Alpha glucosidase
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