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CareCure
鋰及臍帶血細胞

長期以來一直用於治療躁狂抑鬱症患者。最近,香港大學的Yick等[1]報告,鋰可以加強軟骨素酶ABC對大鼠紅核脊髓神經元的再生促進作用,在體內和體外鋰都能強烈刺激臍血單個核細胞(UCBMC)增殖和分泌神經營養因子。

鋰可抑制糖原合成酶激酶3β(GSK3β),GSK3β抑制細胞內上調生長和生存基因的核因子[2],包括Wnt信號[3]、白細胞介素[4]、和其他細胞因子[5]。因此,鋰可以增加幹細胞[6]和T細胞增殖[7],促進神經元分化[8],但阻止神經幹細胞分化[9],增加大鼠腦內因子水平[10],阻止小鼠神經前體細胞凋亡[11],增加小鼠神經祖細胞的增殖[12],加強人神經幹細胞的生存[13]。


臍帶血(UCB)長期以來一直用於治療造血障礙。臍血細胞庫已經有臍血細胞可供使用,找到免疫相容臍血單位的概率較高。臍血安全和有效,從1993年到2006年,全世界已進行逾8000例供體無關臍帶血移植手術。

 

動物研究表明,脊髓損傷後不久即進行臍血細胞移植是有益的。

  • 小鼠ALS模型[14]和大鼠脊髓損傷模型[15]中靜脈輸注人類臍帶血可改善功能;
  • 在不同的大鼠脊髓損傷模型[15-16]和狗脊髓損傷模型[17]在脊髓內移植人CD34+臍血細胞可促進恢復; 
  • 在脊髓內移植人CD34+臍血細胞再加上BDNF可促進受損大鼠脊髓的恢復[18]。

一些研究人員已經報道人類臍帶血(hUCB)可分化成少突膠質細胞和神經元,並促進功能性神經恢復,強烈提示人類臍血作為潛在的脊髓損傷干預治療的可行性和有效性。


最近的研究[19]發現,在體外和體內鋰都能強烈刺激臍血單個核細胞增殖,並分泌神經營養因子。這表明,臍帶血細胞移植加鋰聯合治療在恢復脊髓損傷的功能方面可能較單一治療更有效。


References

1. Yick LW, So KF, Cheung PT and Wu WT (2004). Lithium chloride reinforces the regeneration-promoting effect of chondroitinase ABC on rubrospinal neurons after spinal cord injury. J Neurotrauma. 21:932-43.

2. Phiel CJ and Klein PS (2001). Molecular targets of lithium action. Annu Rev Pharmacol Toxicol. 41:789-813.

3. Etheridge SL, Spencer GJ, Heath DJ and Genever PG (2004). Expression profiling and functional analysis of wnt signaling mechanisms in mesenchymal stem cells. Stem Cells. 22:849-60.

4. Merendino RA, Arena A, Gangemi S, Ruello A, Losi E, Bene A and D'Ambrosio FP (2000).
In vitro interleukin-8 production by monocytes treated with lithium chloride from breast cancer patients. Tumori. 86:149-52.

5. Merendino RA, Mancuso G, Tomasello F, Gazzara D, Cusumano V, Chillemi S, Spadaro P and Mesiti M (1994). Effects of lithium carbonate on cytokine production in patients affected by breast cancer. J Biol Regul Homeost Agents. 8:88-91.

6. De Boer J, Wang HJ and Van Blitterswijk C (2004). Effects of Wnt signaling on proliferation and differentiation of human mesenchymal stem cells. Tissue Eng. 10:393-401.
7. Ohteki T, Parsons M, Zakarian A, Jones RG, Nguyen LT, Woodgett JR and Ohashi PS (2000). Negative regulation of T cell proliferation and interleukin 2 production by the serine threonine kinase GSK-3. J Exp Med. 192:99-104.

8. Kim JS, Chang MY, Yu IT, Kim JH, Lee SH, Lee YS and Son H (2004). Lithium selectively increases neuronal differentiation of hippocampal neural progenitor cells both in vitro and in vivo. J Neurochem. 89:324-36.

9. Aubert J, Dunstan H, Chambers I and Smith A (2002). Functional gene screening in embryonic stem cells implicates Wnt antagonism in neural differentiation. Nat Biotechnol. 20:1240-5.

10. Hellweg R, Lang UE, Nagel M and Baumgartner A (2002).
Subchronic treatment with lithium increases nerve growth factor content in distinct brain regions of adult rats. Mol Psychiatry. 7:604-8.

11. Shimomura A, Nomura R and Senda T (2003).
Lithium inhibits apoptosis of mouse neural progenitor cells. Neuroreport. 14:1779-82.

12. Hashimoto R, Senatorov V, Kanai H, Leeds P and Chuang DM (2003). Lithium stimulates progenitor proliferation in cultured brain neurons. Neuroscience. 117:55-61.

13. Willing AE, Zigova T, Milliken M, Poulos S, Saporta S, McGrogan M, Snable G and Sanberg PR (2002). Lithium exposure enhances survival of NT2N cells (hNT neurons) in the hemiparkinsonian rat. Eur J Neurosci. 16:2271-8.

14. Garbuzova-Davis S, et al. Positive effect of transplantation of hNT neurons (NTera 2/D1 cell-line) in a model of familial amyotrophic lateral sclerosis. Exp Neurol. 2002; 74:169-180

15. Papastefanaki F, et al. Grafts of Schwann cells engineered to express PSA-NCAM promote functional recovery after spinal cord injury. Brain. 130(Pt 8):2159-74, 2007

16. Sparta S, et al. Human umbilical cord blood stem cells infusion in spinal cord injury: engraftment and beneficial influence on behavior. J Hematother Stem Cell Res 12:271-8, 2003

17. Dasari VR, et al. Axonal remyelination by cord blood stem cells after spinal cord injury. J Neurotrauma. 24(2):391-410, 2007

18. Zhao ZM ,et al. Intraspinal transplantation of CD34+ human umbilical cord blood cells after spinal cord hemisection injury improves functional recovery in adult rats. Cell Transplant 13:113-122, 2004

19. Su H, Chu TH, Wu W. Lithium enhances proliferation and neuronal differentiation of neural progenitor cells in vitro and after transplantation into the adult rat spinal cord. Exp Neurol. 2007 Aug;206(2):296-307
 
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