1. Mesenchymal Stem Cells: a new trend for cell therapy
Animal Molecular Physiology Lab
Ran Kim

2. Index Ⅰ. Mesenchymal Stem Cells Ⅱ. Therapeutic mechanisms of MSCs
Ⅲ. MSCs for tumor therapy
Ⅳ. Unsolved problem and challenges
Ⅴ. Summary

3. Stem Cells • unspecialized cells with the ability to renew themselves
• differentiate into various specialized cells
types

4. Stem Cells ESCs ASCs iPSCs type origin blastocyst of embryo
many tissues
reprogramming of somatic cells
strength
pluripotent (3 germ layers)
self-renewal and high replicative capacity
autologous
clinical safety and efficacy data
typically lineage committed
totipotent (3 germ layers and trophoblast)
large reservoir of cells
weakness
immunological concerns
subject to ethical debate
potential for teratoma and teratocarcinoma
currently no clinical trial data
limited number
limited replicative capacity
lineage restricted
no clinical data

5. Ⅰ. Mesenchymal Stem Cells
markers
(+)
CD13, CD29, CD49e, CD54, CD90
(-)
CD14, CD31, CD34, CD45, CD49d, CD106

6. Ⅰ. Mesenchymal Stem Cells
Acta Pharmacol Sin. 2013;34(6):747–754.

7. Ⅱ. Therapeutic mechanisms of MSCs
1. Homing efficiency
The life and fate of mesenchymal stem cells
Cytokine/receptor pair
SDF-1/CXCR4, SCF/c-Kit, HGF/c-Met, VEGF/VEGFR, PDGF/PDGFR, MCP-1/CCR2, HMGB1/RAGE
Front. Immunol. 2014;5:148.

8. Ⅱ. Therapeutic mechanisms of MSCs
Front. Immunol. 2014;5:148.

9. Ⅱ. Therapeutic mechanisms of MSCs
Mol Ther. 2008;16(3):

10. Ⅱ. Therapeutic mechanisms of MSCs
2. Differentiation potential and tissue engineering

11. Ⅱ. Therapeutic mechanisms of MSCs
3. Product of trophic factors
J Cell Biochem. 2006;98(5):

12. Ⅱ. Therapeutic mechanisms of MSCs
4. immunomodulation
Immunomodulatory properties of mesenchymal stromal cells
Blood. 2007;110(10):

13. Ⅲ. MSCs for tumor therapy
1. MSC delivery of interleukins
Blood 2013;122:e23-e32

14. Ⅲ. MSCs for tumor therapy
Cytokine Gene-engineered MSCs
• AdIL-12-engineered MSCs significantly
suppressed tumor growth and enhanced weight loss
• AdIL-12-MSC therapy resulted in significant
increment of apoptotic index versus controls.
A tumor-selective biotherapy with prolonged impact on established metastases based on cytokine gene-engineered MSCs.
Mol Ther. 2008;16(4):

15. Ⅱ. MSCs for tumor therapy
2. Interferons
INF-β: anti-proliferative and proapoptotic effect
 Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors
Cancer Res. 2002;62(13):

16. Ⅲ. MSCs for tumor therapy
3. Prodrug
a medication or compound that, after administration, is metabolized (i.e., converted within the body) into a pharmacologically active drug
Mol Ther. 2010;18(1):

17. Ⅲ. MSCs for tumor therapy
4. oncolytic viruses
5. antiangiogenic agents
6. Pro-apoptotic proteins
Viruses. 2015;7(12):

18. Ⅳ. Unsolved problem and challenges
• interactions between MSCs and the inflammatory milieu in which they reside and the therapeutic mechanisms of MSCs
• which source should be used for which disease, which route of administration is best suited for a particular disease
• the parameters for monitoring clinical effectiveness
• established standards for cell expansion protocols, product quality, and safety controls
• establish regulatory polices to meet the challenges of this newly emerging and rapidly advancing field and benefit patients suffering a wide array of diseases.

19. Ⅴ. Summary
Acta Pharmacol Sin.2013;34(6):747–754.