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Cord Blood and Lithium Therapy of Spinal Cord Injury (SCI)

May 2012
Wise Young, PhD MD
Dr. Wise Young photo

Wise Young, Ph.D. M.D.
Richard H. Shindell Chair
in Neuroscience at
Rutgers University

Umbilical cord blood (UCB) contains many stem cells per volume, more than adult bone marrow. In the past 20 years, UCB transplants have saved thousands of people suffering from disorders of the blood and immune system. Since 2005, UCB transplants are known to cure Krabbe's disease [1], a neurological disease that prevents myelination, and a variety of metabolic disorders [2]. Many researchers have reported that UCB may be beneficial for acquired neurological conditions such as stroke [3-4] and cerebral palsy [5-6].

Cord blood is stored in two types of banks: public or private (family). The former hold cord blood donated for the purposes of transplantation to other people, and are strictly regulated by the U.S. Food and Drug Administration (FDA). The latter are cord blood stored by families for private use by the donor. In general, the quality of privately banked cord blood is significantly lower in family banks [6]. On the other hand, autologous (self) cord blood units should have the best immunological match. Patients who did not store their own cord blood can utilize HLA-matched units from public banks.

UCB transplants improved recovery in rat [7-11] and dog [12-15] SCI models. UCB cells may help injured spinal cords through a variety of mechanisms [16-21], including stimulating myelination, suppressing inflammation, and preventing cell death. Studies have shown that various populations of stem cells in the UCB are all effective. These include unfractionated mono-nuclear cells in UCB [22-26], CD34+ cells [8, 27-29], multipotent cells cultured from UCB [10], mesenchymal stem cells [30-33], CD133+ pluripotent stem cells [34], and cultured neuron-like UCB cells [35], as well as UCB cells genetically modified to make neurons [36, 37] and to secrete growth factors [38, 39].

Lithium stimulates spinal cord regeneration [41-42] and stem cell proliferation in rats after SCI [43-44]. Lithium is the reference therapy for manic depression, taken by over 30 million people around the world. Lithium stimulates bone marrow and neural stem cells [44] to proliferate and to produce growth factors [45]. In humans, lithium significantly increases the brain's gray matter volume [46]. We therefore proposed that the UCB stem cells and lithium have synergistic effects on SCI recovery.

The China Spinal Cord Injury Network (ChinaSCINet) formed in 2006 to test promising SCI therapies. The network has 24 leading SCI centers in China, Hong Kong, and Taiwan. The clinical trials in the network are testing injections of UCB stem cells into the spinal cord and oral lithium treatment, individually and in combination, in patients with chronic (>1yr) and subacute (2day - 2week) SCI (Table 1). The UCB given to patients come from donors that match at least 4 out of 6 recipient HLA. These UCB are donated by the cord blood bank StemCyte.



Table 1. ChinaSCINet trials


NameSCINo.Treatment GroupsComments
CN101>1yr206w oral lithium carbonate (Li, titrated to 0.8-1.0 mM in serum)Phase 1 open label, adverse events
CN102A>1yr40Placebo vs. 6w of Li (0.8-1.2 mM serum levels)Phase 2 randomized double blind
CN102B>1yr40A-C: 4, 8, or 16 μl x4 (100,000 cells/ μl) UCB transplants; D. 16 μliter cells with MP; E. 16 μliter cells with MP + LiPhase 2 escalating dose, randomized, open label, ASIA motor/sensory scores
CN102C2day- 2wk40A: Surgery; B: 6w of Li; C: 4x 16 μliters UCB; D: UCB +LiPhase 2 randomized double blind, ongoing
CN103>1yr400UCB vs UCB + 6w oral Li (stratified ASIA A, B, C)Phase 3 randomized double blind, 2013


Legend: Oral lithium carbonate is increased every 3 days until serum Li >0.6 and <1.0 mM. Escalating doses of UCBMC (4, 8, or 16 μl of 100,000 cells/ μl) are injected into dorsal root entry zones above and below the injury site. MP is 30 mg/kg methylprednisolone given intravenously.



ChinaSCINet is conducting five clinical trials to establish the safety and feasibility of UCB and lithium treatments of SCI. CN101 showed that lithium is safe for patients with chronic SCI [47]. CN102A revealed no difference in neurological improvement between chronic SCI patients who received lithium or a placebo, but lithium reduced neuropathic pain [48]; a follow-up phase 3 trial is planned. CN102B has to date transplanted 28 patients (8 in Hong Kong, 20 in Kunming) and CN102C has randomized 30 subjects. CN103 is a phase 3 trial aimed at ascertaining whether UCB with or without lithium improves recovery.


In summary, the goal of ChinaSCINet is to conduct clinical trials of promising therapies for SCI. So far, UCB transplants appear to be safe and some subjects are regaining sensory and motor function. We plan to initiate phase 3 trials in 2013 in China, USA, Norway, and India. ChinaSCINet will continue to study promising therapies and compare them against the best therapy found in CN103.

Wise Young PhD MD is the Richard H. Shindell Chair of Neuroscience at Rutgers University in New Jersey. He founded and directs ChinaSCINet. He also serves as voluntary (unpaid) Global Medical Director of Stemcyte, Inc.


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