| | ENG


intranet.jpg
仅供研究人员使用




CareCure
锂及脐带血细胞

长期以来一直用于治疗躁狂抑郁症患者。最近,香港大学的Yick等[1]报告,锂可以加强软骨素酶ABC对大鼠红核脊髓神经元的再生促进作用,在体内和体外锂都能强烈刺激脐血单个核细胞(UCBMC)增殖和分泌神经营养因子。

锂可抑制糖原合成酶激酶3β(GSK3β),GSK3β抑制细胞内上调生长和生存基因的核因子[2],包括Wnt信号[3]、白细胞介素[4]、和其他细胞因子[5]。因此,锂可以增加干细胞[6]和T细胞增殖[7],促进神经元分化[8],但阻止神经干细胞分化[9],增加大鼠脑内因子水平[10],阻止小鼠神经前体细胞凋亡[11],增加小鼠神经祖细胞的增殖[12],加强人神经干细胞的生存[13]。


脐带血(UCB)长期以来一直用于治疗造血障碍。脐血细胞库已经有脐血细胞可供使用,找到免疫相容脐血单位的概率较高。脐血安全和有效,从1993年到2006年,全世界已进行逾8000例供体无关脐带血移植手术。

 

动物研究表明,脊髓损伤后不久即进行脐血细胞移植是有益的。

  • 小鼠ALS模型[14]和大鼠脊髓损伤模型[15]中静脉输注人类脐带血可改善功能;
  • 在不同的大鼠脊髓损伤模型[15-16]和狗脊髓损伤模型[17]在脊髓内移植人CD34+脐血细胞可促进恢复; 
  • 在脊髓内移植人CD34+脐血细胞再加上BDNF可促进受损大鼠脊髓的恢复[18]。

一些研究人员已经报道人类脐带血(hUCB)可分化成少突胶质细胞和神经元,并促进功能性神经恢复,强烈提示人类脐血作为潜在的脊髓损伤干预治疗的可行性和有效性。


最近的研究[19]发现,在体外和体内锂都能强烈刺激脐血单个核细胞增殖,并分泌神经营养因子。这表明,脐带血细胞移植加锂联合治疗在恢复脊髓损伤的功能方面可能较单一治疗更有效。


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
 
Copyright © 2007. CHINASCINET
关于我们 | 脊髓损伤 | 临床研究 | 活动情况 | 学术大会 | 联系我们