Hanyang Med Rev.  2012 Aug;32(3):159-162. 10.7599/hmr.2012.32.3.159.

Strategy for Maximizing Therapeutic Efficacy of Adult Stem Cells

• Koh SH

• KMID: 1436772
• DOI: http://doi.org/10.7599/hmr.2012.32.3.159

Abstract

Stem cells have been suggested for the treatment of intractable neurological diseases. In spite of numerous clinical trials using autologous mesenchymal stem cells (MSCs), unfortunately, clinical efficacy has not yet been proved except for its safety. Although there are several reasons for unsuccessful efficacy of stem cell therapy using adult stem cells, we should consider the exact factors that may improve the therapeutic efficacy of adult stem cells. One of the most important factors is the patient's age when MSCs are obtained from patients. It is associated with decreased functions of MSCs. Several reports have shown that MSCs from elderly persons have decreased capacities in the secretion of neurotrophic factors and migration to the lesion site. Therefore, procedures potentiating MSCs need to be studied during ex-vivo expansion. To suggest diverse procedures to improve capacities of MSCs for improvement of therapeutic efficacy, I will discuss previously reported methods potentiating MSCs and will suggest further experiments.

Keyword

Neurodegenerative Diseases; Stem Cells; Tissue Therapy

MeSH Terms

Adult
Adult Stem Cells
Aged
Humans
Mesenchymal Stromal Cells
Nerve Growth Factors
Neurodegenerative Diseases
Stem Cells
Tissue Therapy
Nerve Growth Factors

Reference

1. Boncoraglio GB, Bersano A, Candelise L, Reynolds BA, Parati EA. Stem cell transplantation for ischemic stroke. Cochrane Database Syst Rev. 2010. CD007231.

2. Lee JS, Hong JM, Moon GJ, Lee PH, Ahn YH, Bang OY. A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells. 2010. 28:1099–1106.

3. Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2012. 3:CD001447.

4. Gamez J, Carmona F, Raguer N, Ferrer-Sancho J, Martin-Henao GA, Marti-Beltran S, et al. Cellular transplants in amyotrophic lateral sclerosis patients: an observational study. Cytotherapy. 2010. 12:669–677.

5. Soler B, Fadic R, von Bernhardi R. Stem cells therapy in amyotrophic lateral sclerosis treatment. A critical view. Rev Neurol. 2011. 52:426–434.

6. Venkataramana NK, Kumar SK, Balaraju S, Radhakrishnan RC, Bansal A, Dixit A, et al. Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson's disease. Transl Res. 2010. 155:62–70.

7. Politis M, Lindvall O. Clinical application of stem cell therapy in Parkinson's disease. BMC Med. 2012. 10:1.

8. Lee HJ, Lee JK, Lee H, Shin JW, Carter JE, Sakamoto T, et al. The therapeutic potential of human umbilical cord blood-derived mesenchymal stem cells in Alzheimer's disease. Neurosci Lett. 2010. 481:30–35.

9. Stolzing A, Jones E, McGonagle D, Scutt A. Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev. 2008. 129:163–173.

10. Koh SH, Baik W, Noh MY, Cho GW, Kim HY, Kim KS, et al. The functional deficiency of bone marrow mesenchymal stromal cells in ALS patients is proportional to disease progression rate. Exp Neurol. 2012. 233:472–480.

11. Cho GW, Noh MY, Kim HY, Koh SH, Kim KS, Kim SH. Bone marrow-derived stromal cells from amyotrophic lateral sclerosis patients have diminished stem cell capacity. Stem Cells Dev. 2010. 19:1035–1042.

12. Koh SH, Huh YM, Noh MY, Kim HY, Kim KS, Lee ES, et al. Beta-PIX is critical for transplanted mesenchymal stromal cell migration. Stem Cells Dev. 2012. 21:1989–1999.

13. Lu Z, Hu X, Zhu C, Wang D, Zheng X, Liu Q. Overexpression of CNTF in Mesenchymal Stem Cells reduces demyelination and induces clinical recovery in experimental autoimmune encephalomyelitis mice. J Neuroimmunol. 2009. 206:58–69.

14. Yang C, Zhou L, Gao X, Chen B, Tu J, Sun H, et al. Neuroprotective effects of bone marrow stem cells overexpressing glial cell line-derived neurotrophic factor on rats with intracerebral hemorrhage and neurons exposed to hypoxia/reoxygenation. Neurosurgery. 2011. 68:691–704.

15. Cho GW, Koh SH, Kim MH, Yoo AR, Noh MY, Oh S, et al. The neuroprotective effect of erythropoietin-transduced human mesenchymal stromal cells in an animal model of ischemic stroke. Brain Res. 2010. 1353:1–13.

16. Tsai LK, Wang Z, Munasinghe J, Leng Y, Leeds P, Chuang DM. Mesenchymal stem cells primed with valproate and lithium robustly migrate to infarcted regions and facilitate recovery in a stroke model. Stroke. 2011. 42:2932–2939.

17. Koh SH, Noh MY, Cho GW, Kim KS, Kim SH. Erythropoietin increases the motility of human bone marrow-multipotent stromal cells (hBM-MSCs) and enhances the production of neurotrophic factors from hBM-MSCs. Stem Cells Dev. 2009. 18:411–421.

18. Rosova I, Dao M, Capoccia B, Link D, Nolta JA. Hypoxic preconditioning results in increased motility and improved therapeutic potential of human mesenchymal stem cells. Stem Cells. 2008. 26:2173–2182.

19. Yang DC, Yang MH, Tsai CC, Huang TF, Chen YH, Hung SC. Hypoxia inhibits osteogenesis in human mesenchymal stem cells through direct regulation of RUNX2 by TWIST. PLoS One. 2011. 6:e23965.

20. Liu L, Yu Q, Lin J, Lai X, Cao W, Du K, et al. Hypoxia-inducible factor-1alpha is essential for hypoxia-induced mesenchymal stem cell mobilization into the peripheral blood. Stem Cells Dev. 2011. 20:1961–1971.

21. Leroux L, Descamps B, Tojais NF, Seguy B, Oses P, Moreau C, et al. Hypoxia preconditioned mesenchymal stem cells improve vascular and skeletal muscle fiber regeneration after ischemia through a Wnt4-dependent pathway. Mol Ther. 2010. 18:1545–1552.

22. Saito K, Fukuda N, Matsumoto T, Iribe Y, Tsunemi A, Kazama T, et al. Moderate low temperature preserves the stemness of neural stem cells and suppresses apoptosis of the cells via activation of the cold-inducible RNA binding protein. Brain Res. 2010. 1358:20–29.