Stem Cell Therapy: Sources, Reprogramming Process, and Biomimetic Scaffolding

This presentation discusses stem cell therapy, its sources, reprogramming process, and biomimetic scaffolding. It explores the potential of stem cell therapy in regenerative medicine and its limitations. The presentation also highlights ethical issues related to stem cell therapy. References are provided for further reading.

STEM CELL THERAPY
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Introduction
 Stem cell are widely used in regenerative medicine, hence stem cell
therapy.
 SC therapy entails reprogramming and transplantation of ESC, NSC, iPSCs.
 SC therapy exploits the regenerative, renewal and development of the
stem cells to remedy damaged tissues and organs. Therefore, used in
treatment of degenerative diseases such as multiple sclerosis (Rusu et al.,
2016).
 The sources of the SCs include; hematopoietic, mesenchymal, epithelial
and neural cells (Liu et al., 2016).
 The iPSCs are manipulated in vitro differentiating into desired cell types.

The ESCs
They are primary sources of SCs due to their pluripotency (Rusu et al., 2016).
Pluripotency is the ability to proliferate and transform cells into somatic cells.
Obtained from early phases of a developing embryo.
Also, from the inner mass of cells of an embryo
Have the ability to form the ectoderm, mesoderm and endoderm of the germ cell.
Applied in treatment of neurological disorders and pancreatic problems.
Ethical issue: May initiate formation of tumor cells called teratoma
Limitation: Immunogenicity during transplant

Non-embryonic SCs
Referred to as adult SCs, common cell type is the MSC.
They are obtained from adult somatic tissues for example, bone
marrow
Have high proliferation ability and improved colony forming activity.
They can develop into more than one lineages when applied alongside
endometrial SCs
They secrete many bioactive molecules known as growth factors.
Do not cause immunological issues hence used in treatment of the
MHC-unmatched immunosuppression.

The hiPSCs
• Research by Takahashi and Yamanaka showed conversion of adult somatic mice fibroblastic
cells into SCs.
• These cells have similar characteristics with the ESCs.
• Four transcription genes (Oct3/4, Sox2, Myc and Klf4) known as reprogramming factors though
a retroviral mechanism are used in the conversion.
• Apart from treatment of regenerative diseases, they have an application in drug development,
disease modelling and toxicity tests.
• They are obtained from dermal fibroblasts among many other sources such as kidney mesangial
cells (Rusu et al., 2016).
• Faces safety and efficacy issues.
• Studies depict promising breakthrough in the treatment of diseases such as spinal cord injury.

The Reprogramming process
• The SCs require to form a microenvironment called ‘niche’ to sustain themselves.
• It is a stepwise process starting at the initiation phase, maturation and ends at the
stabilization phase.
• Initiation; losing of somatic cell program, increased proliferation, metabolic
alteration, morphological changes, inhibition of apoptosis and senescence.
• Maturation; acquiring of pluripotency-associated genes
• Stabilization; telomerase elongation, x-reactivation, loss of epigenetic memory,
independent auto-renewal and pluripotency.
• The stages occur through somatic-cell reprogramming pathways such as TGF-
cascade.

Biomimetic Scaffolding
• The biomimetic signaling pathway activates the differentiation
of the SCs
• The scaffolds are constructed in vitro forming 3_D tissues and
organs
• They are both natural and synthetic polymers.
• Natural polymers are biodegradable polysaccharide or protein
having a similar morphology with the native cell's extracellular
matrix.

Biomimetic scaffolds continued…
• They reduce immunogenicity due to their enhanced
biocompatibility.
• Limitation; their mechanical and biodegradable properties are
limited
• Synthetic polymers such as polyglycolic acid are regulated by
varying the polymer itself.
• They are broadly applied in surgery for bone reconstruction
(Rusu et al., 2016).

Conclusion
• The self-renewal of the iPSC, ESC and MSC are important for
regenerative medicine.
• These therapy has succefully been applied before in the treatment of fatal
diseases such as hematological dysfunctions.
• Ethical issue related to their application such as teratoma formation derail
its extensive application.

References
• Drug Discovery - Newcells Biotech. (2018). Retrieved from
https://newcellsbiotech.co.uk/drug-discovery/
• Gaipov, A., & Myngbay, A. (2018). Stem Cells Therapy in General
Medicine. European Journal of General Medicine, 15(2), 50-53.
doi:10.29333/ejgm/83014
• Liu, S., Zhou, J., Zhang, X., Liu, Y., Chen, J., Hu, B., ... & Zhang, Y. (2016).
Strategies to optimize adult stem cell therapy for tissue regeneration. International
journal of molecular sciences, 17(6), 982.
• Rusu, E., Necula, L. G., Neagu, A. I., Alecu, M., Stan, C., Albulescu, R., & Tanase, C.
P. (2016). Current status of stem cell therapy: opportunities and limitations. Turkish
Journal of Biology, 40(5), 955-967.