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Thread: A review of umbilical cord blood transplant effects on brain and spinal cord injury

  1. #1

    A review of umbilical cord blood transplant effects on brain and spinal cord injury

    Many animal studies have reported beneficial effects of umbilical cord blood (UCB) transplants to the brain and spinal cord, and a variety other conditions. The work has been reviewed several times recently [1-4]. We are still in the midst of our studies and cannot talk about our results yet. So, let me review some of the work suggesting that UCB transplants may be beneficial in brain and spinal cord injury.

    Spinal cord injury. Several studies support the beneficial effects of UCB on spinal cord injury in animal studies. Several groups are beginning to transplant the cells into the spinal cord [5].
    • In 2005, Kuh, et al. [6] transplanted human UCB into the spinal cord of rats. One group received UCB cells only, one group received UCB cells and the neurotrophin BDNF, and one group received only media (control). They report that the transplanted cells differentated into various neural cells and combination UCB+BDNF had the best locomotor recovery (BBB scores).
    • In 2004, Zhao, et al. [7] transplanted CD34+ human UCB cells into hemisected rat spinal cords, compared to human bone marrow stem (BMS) cells. Rats that received the CD34+ UCB cells had better functional scores than those that received BMS cells at 7 and 14 days. Histological evaluation showed labeled human UCB and BMS cells in the spinal cord.
    • In 2004, Li, et al. [8] transplanted human CD34+ UCB cells labelled by BRDU into hemisected rat spinal cords. The UCB treated rats had better locomotor recovery. They found that the cells survived and 2% of the cells showed neuronal markers and 7% expressed astrocytic markers.
    • In 2003, Saporta, et al. [9] infused human UCB cells intravenously in rats after a clip compression injury of the spinal cord at 1 or 5 days after injury. Rats treated with human UCB cells at 5 days showed significant better functional recovery than those treated at 1 day or not treated.

    Stroke. More studies support the beneficial effects of UCB on stroke. I will only review some studies from the last two years.
    • In 2006, Meier, et al. [10] reported that human UCB mononuclear cells given intraperitoneally will incorporate into damaged brain areas and alleviate the neurological effects of a rat model of perinatal brain damage. The treatment apparently alleviated spastic paresis and restored walking in the rats. The cells entering the brain do not, however, differentiate into neural cells. Chen, et al. [11] infused human UCB into rats 24 hours after initiation of heatstroke. Compared to human peripheral blood mononuclear cells (PBMC), pretreatment of the rats with human UCB reduced heatstroke induced hypotention, cerebral ischemia and hypoxia, and iNOS-dependent NOS levels. The human UCB entered the brain. The authors suggested that human UCB transplants may be useful for prevening heatstroke.
    • In 2005 Xiao, et al. [12] isolated a novel line of cells from human UCB that express stem cell markers Oct-4, Rex-1, and Sox-2. They injected these cells into rats 48 hours after transient unilaeral middle cerebral artery occlusion, comparing these against a neural stem cell line (RN33b). They found that UCB treated ras recovered better mean behavioral recovery scores and better stepping tests, and had a 50% reduction in lesion volume compared to saline-treated rats.
    • In 2005, Vendrame, et al. [13, 14] treated rats with human UCB after middle cerebral artery occlusion. The UCB transplanted rats showed reduced RNA and protein expression of pro-inflammatory cytokines and NF-kappaB in the brain. The authors pointed out that although UCB is thought of as a “cell replacement therapy”, they propose that the cells have an anti-inflammatory and neuroprotective effect in stroke.
    • In 2005, Pan, et al. [15] transplanted freshly isolated human UCB cells displaying CD33, CD44, CD45, CD51/61, and CD90/Thy-1 into the brains of rats with and without cyclosporin, up to 14 days. Most of the cells localized within 500 microns of the injection site but a subpopulation migrated along the corpus callosum. Cell survival was similar regardless whether the cells were fresh or cultured, and whether cyclosporin was given. They found weak upregulation of major histocompatibility antigens (MHC) class I antigens in all animals but cyclosporin reduced the number of cells expressing MHC class II antigens. [Please note that immunorejection is delayed in the brain and cells usually survive for 4 weeks or longer, explaining why there is no difference between cyclosporin and non-cyclosporin treated rats].
    • In 2005, Newman, et al. [16] reported that human UCB cells tended to migrate towards rat brain tissues harvested at 24-72 hours after sroke. They suggest that chemokines present in ischemic brain attract human UCB cells.
    • In 2005, Nan, et al. [17] infused human UCB cells into rats at 24 hours after brain damage due to intracerebral hemorrhage. They report that the rats performed better in neurological tests at 6 and 13 days after treatment. They conclude that human UCB cells may be neuroprotective.

    Several studies suggest that umbilical cord blood may be beneficial for oher conditions. For example, in 2006, Ende & Reddi [18] suggest administration of human UCB mononuclear cells to type 1 and type 2 diabetic mice improves blood glucose levels and survival. They suggest transfusion of HUCB to low birth weight infans to prevent laer development of type 2 diabetes. In 2003, Garbuzova-Davis, et al. [19] reports that human UCB given intravenously to mice with ALS will migrate into the spinal cord and express neural markers and astrocytic markers. The mice showed delayed progression of disease for 2-3 weeks and had increased life-span compared to untrated mice.

    References cited

    1. Sanberg PR, Willing AE, Garbuzova-Davis S, Saporta S, Liu G, Sanberg CD, Bickford PC, Klasko SK and El-Badri NS (2005). Umbilical cord blood-derived stem cells and brain repair. Ann N Y Acad Sci. 1049:67-83. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15965108
    2. Newman MB, Emerich DF, Borlongan CV, Sanberg CD and Sanberg PR (2004). Use of human umbilical cord blood (HUCB) cells to repair the damaged brain. Curr Neurovasc Res. 1:269-81. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16181077
    3. Newman MB, Davis CD, Kuzmin-Nichols N and Sanberg PR (2003). Human umbilical cord blood (HUCB) cells for central nervous system repair. Neurotox Res. 5:355-68. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=14715454
    4. Sanberg PR, Willing AE and Cahill DW (2002). Novel cellular approaches to repair of neurodegenerative disease: from Sertoli cells to umbilical cord blood stem cells. Neurotox Res. 4:95-101. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=12829408
    5. Roussos I, Rodriguez M, Villan D, Ariza A, Rodriguez L and Garcia J (2005). Development of a rat model of spinal cord injury and cellular transplantation. Transplant Proc. 37:4127-30. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16386643
    6. Kuh SU, Cho YE, Yoon DH, Kim KN and Ha Y (2005). Functional recovery after human umbilical cord blood cells transplantation with brain-derived neutrophic factor into the spinal cord injured rat. Acta Neurochir (Wien). 147:985-92. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16010451
    7. Zhao ZM, Li HJ, Liu HY, Lu SH, Yang RC, Zhang QJ and Han ZC (2004). Intraspinal transplantation of CD34+ human umbilical cord blood cells after spinal cord hemisection injury improves functional recovery in adult rats. Cell Transplant. 13:113-22. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15129757
    8. Li HJ, Liu HY, Zhao ZM, Lu SH, Yang RC, Zhu HF, Cai YL, Zhang QJ and Han ZC (2004). [Transplantation of human umbilical cord stem cells improves neurological function recovery after spinal cord injury in rats]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 26:38-42. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15052772
    9. Saporta S, Kim JJ, Willing AE, Fu ES, Davis CD and Sanberg PR (2003). 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. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=12857368
    10. Meier C, Middelanis J, Wasielewski B, Neuhoff S, Roth-Haerer A, Gantert M, Dinse HR, Dermietzel R and Jensen A (2006). Spastic paresis after perinatal brain damage in rats is reduced by human cord blood mononuclear cells. Pediatr Res. 59:244-9. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16439586
    11. Chen SH, Chang FM, Tsai YC, Huang KF, Lin CL and Lin MT (2006). Infusion of human umbilical cord blood cells protect against cerebral ischemia and damage during heatstroke in the rat. Exp Neurol. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16405889
    12. Xiao J, Nan Z, Motooka Y and Low WC (2005). Transplantation of a novel cell line population of umbilical cord blood stem cells ameliorates neurological deficits associated with ischemic brain injury. Stem Cells Dev. 14:722-33. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16433627
    13. Vendrame M, Gemma C, de Mesquita D, Collier L, Bickford PC, Sanberg CD, Sanberg PR, Pennypacker KR and Willing AE (2005). Anti-inflammatory effects of human cord blood cells in a rat model of stroke. Stem Cells Dev. 14:595-604. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16305344
    14. Vendrame M, Cassady J, Newcomb J, Butler T, Pennypacker KR, Zigova T, Sanberg CD, Sanberg PR and Willing AE (2004). Infusion of human umbilical cord blood cells in a rat model of stroke dose-dependently rescues behavioral deficits and reduces infarct volume. Stroke. 35:2390-5. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15322304
    15. Pan Y, Nastav JB, Zhang H, Bretton RH, Panneton WM and Bicknese AR (2005). Engraftment of freshly isolated or cultured human umbilical cord blood cells and the effect of cyclosporin A on the outcome. Exp Neurol. 192:365-72. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15755554
    16. Newman MB, Willing AE, Manresa JJ, Davis-Sanberg C and Sanberg PR (2005). Stroke-induced migration of human umbilical cord blood cells: time course and cytokines. Stem Cells Dev. 14:576-86. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16305342
    17. Nan Z, Grande A, Sanberg CD, Sanberg PR and Low WC (2005). Infusion of human umbilical cord blood ameliorates neurologic deficits in rats with hemorrhagic brain injury. Ann N Y Acad Sci. 1049:84-96. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15965109
    18. Ende N and Reddi AS (2006). Administration of human umbilical cord blood to low birth weight infants may prevent the subsequent development of type 2 diabetes. Med Hypotheses. 66:1157-60. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16481120
    19. Garbuzova-Davis S, Willing AE, Zigova T, Saporta S, Justen EB, Lane JC, Hudson JE, Chen N, Davis CD and Sanberg PR (2003). Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: distribution, migration, and differentiation. J Hematother Stem Cell Res. 12:255-70. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=12857367
    Last edited by Wise Young; 04-07-2006 at 08:22 AM.

  2. #2
    We are still in the midst of our studies and cannot talk about our results yet. So, let me review some of the work suggesting that UCB transplants may be beneficial in brain and spinal cord injury.

    Hmmm, so the results look promising.

    Rats treated with human UCB cells at 5 days showed significant better functional recovery than those treated at 1 day or not treated.
    Interesting for chronics.

  3. #3
    Banned Faye's Avatar
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    Where are the walking rats video'a after UCB stem cell treatments

    Dr. Young, I have no doubt that UCB stem cell treatment "ameliorates neurologic deficits in rats", however I could not find any indication that the UCB treatments in rats resored walking ability in rats, unlike Keirsted's work.

    Example:
    Spinal Cord Injury; Umbilical Cord Blood Transplantation Improves Mobility After Spinal Cord Injury
    Stem Cell Week
    20 March 2006

    2006 MAR 20 - (NewsRx.com) -- Umbilical cord blood transplantation improves mobility in rats with spinal cord injury.

    According to a study from Spain, "Intravenously or intraspinally delivered human umbilical cord blood (UCB) cells and mesenchymal stem cells have been previously shown to improve the functional recovery of spinal cord-injured rats. Obtaining an animal model in the laboratory setting is critical for the development of experimental therapies."

    "We have established a rat model of spinal cord injury (SCI) with basic histological and functional evaluations, ready to use for cell transplantation experiments.

    "In the first phase 10 Sprague-Dawley (SD) rats were used to standardize the laminectomy at D9-D10 without secondary lesions. In a second phase," wrote I. Roussos and colleagues at Hospital Duran Reynals in Barcelona, "28 SD rats were laminectomized and injured at D9 by spinal cord compression for 3 to 5 seconds with an aneurysmal clip."

    "Open-field behavior was assessed at days 2 and 7 postoperatively, and weekly until their sacrifice, using the Basso, Beattie, and Bresnahan locomotor rating scale. Two weeks postinjury, 14 immunosuppressed rats received a double intraspinal cell transplant of previously frozen UCB mononuclear cells (MNCs).

    "Using a Hamilton syringe," continued the authors, "2.5x105 unlabelled MNCs in 10 mcL medium were transplanted, rostrally and caudally to the lesion site. Rats were sacrificed at 4 weeks posttransplant by transcardial perfusion with 4% paraformaldehyde, and spinal cords were dissected and further fixated for histological analysis. No wound infections were observed."

    Investigators reported, "Thirteen rats developed urinary tract infections and two animals showed autophagia grade 3. We observed a common spontaneous mobility improvement until a certain limit, depending on the degree of lesion and intrinsic characteristics of the animal. An animal model of SCI has been established."
    http://www.stemcellnews.com/articles...ord-injury.htm

    I think these folks would be the first to tout such feat ( walking rats after UCB stem cell treatment ) if it existed:

    http://www.physiciansforlife.org/ind...sk=view&id=890

    "There’s far too much unthinking respect given to authority,” Molly Ivins explained; “What you need is sustained outrage.”
    Kerr, Keirstead, McDonald, Stice and Jun Yan courageously work on ESCR to Cure SCI.

    Divisiveness comes from not following Christopher Reeve's ESCR lead.
    Young does ASCR.
    [I]I do not tear down CRPA, I ONLY make peopl

  4. #4
    Faye,

    If you click on the links provided in my summary below (in the references), you can read the abstracts of the papers. I pulled out some of the spinal cord injury references for you here. Admittedly, these are not the best of papers but they do provide interesting reading. I went to some trouble summarizing the stroke literature for you because I know that your son Jason had a brainstem stroke.

    Wise.



    • Zhao ZM, Li HJ, Liu HY, Lu SH, Yang RC, Zhang QJ and Han ZC (2004). Intraspinal transplantation of CD34+ human umbilical cord blood cells after spinal cord hemisection injury improves functional recovery in adult rats. Cell Transplant 13: 113-22. The present study was designed to compare the functional outcome of the intraspinal transplantation of CD34+ human umbilical cord blood (CB) cells with that of human bone marrow stromal (BMS) cells in adult rats with spinal cord injury. Sixty adult Wistar rats were subjected to left spinal cord hemisection, and then divided into three groups randomly. The control group received an injection of PBS without cells, while the two other groups of rats received a transplantation of 5 x 10(5) CD34+ CB or BMS cells, respectively. Functional outcome was measured using the modified Tarlov score at days 1, 7, 14, 21, and 28 after transplantation. A statistically significant improvement in functional outcome and survival rate in the experimental groups of rats was observed compared with the control group. Rats that received CD34+ CB cells achieved a better improvement in functional score than those that received BMS cells at days 7 and 14 after transplantation. Histological evaluation revealed that bromodeoxyuridine (BrdU)-labeled CD34+ CB and BMS cells survived and migrated into the injured area. Some of these cells expressed glial fibriliary acidic protein (GFAP) or neuronal nuclear antigen (NeuN). Our data demonstrate for the first time that intraspinal transplantation of human CD34+ CB cells provides benefit in function recovery after spinal cord hemisection in rats and suggest that CD34+ CB cells may be an excellent choice of cells as routine starting material of allogenic and autologous transplantations for the treatment of spinal cord injury. National Research Center for Stem Cell Engineering & Technology, State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin, People's Republic of China. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15129757
    • Li HJ, Liu HY, Zhao ZM, Lu SH, Yang RC, Zhu HF, Cai YL, Zhang QJ and Han ZC (2004). [Transplantation of human umbilical cord stem cells improves neurological function recovery after spinal cord injury in rats]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 26: 38-42. OBJECTIVE: To study whether intraspinally transplanted human cord blood CD34+ cells can survive, differentiate, and improve neurological functional recovery after spinal cord injury in rats. METHODS: Rats were randomly divided into two groups. One group of rats was subjected to spinal cord left-hemisection and transplanted with human cord blood CD34+ cells labeled by bromodeoxyuridine (BrdU); The other group was carried by left-hemisection with injection of PBS (control group). The neurological function was determined before and 24 h, 1, 2, 3 and 4 weeks after spinal cord injury and cell transplantation using the modified Tarlov score. The distribution and differentiation of transplanted human cord blood cells in vivo in rat spinal cord were evaluated by histological and immnuhistochemical analysis. RESULTS: Functional recovery determined by modified Tarlov score was significantly improved in the group receiving human cord blood CD34+ cells compared with the control group (P < 0.05). Moreover, human cord blood CD34+ cells were found to survive in rat spinal cord microenvironment, with the expression of the neural nuclear specific protein (NeuN) in 2% BrdU-reactive human cells and of the astrocytic specific protein glial fibrillary acidic protein (GFAP) in 7% BrdU-reactive human cells. CONCLUSIONS: Intraspinally administered human cord blood CD34+ cells can survive, differentiate, and improve functional recovery after spinal cord injury in rats. Transplantation of human cord blood cells may provide a novel strategy for the treatment of neural injury. State Key Laboratory of Experimental Hematology, Institute of Hematology, CAMS and PUMC, Tianjin 300020, China. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=15052772
    • Saporta S, Kim JJ, Willing AE, Fu ES, Davis CD and Sanberg PR (2003). 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. The use of human umbilical cord blood (hUCB)--a rich source of nonembryonic or adult stem cells--has recently been reported to ameliorate behavioral consequences of stroke. In this study, we tested whether human cord blood leukocytes also ameliorate behavioral impairments of spinal cord injury. Rats were divided into five groups: (1) laminectomy (without spinal cord injury) only; (2) laminectomy + cord blood infusion; (3) spinal cord injury + cord blood infused 1 day post injury; (4) spinal cord injury + cord blood infused 5 days post injury; and (5) spinal cord injury only. Spinal cord injury was induced by compressing the spinal cord for 1 min with an aneurysm clip calibrated to a closing pressure of 55 g. Open-field behavior was assessed 1, 2, and 3 weeks after intravenous injection of prelabeled human cord blood cells. Open-field test scores of spinal cord injured rats treated with human cord blood at 5 days were significantly improved as compared to scores of rats similarly injured but treated at day 1 as well as the otherwise untreated injured group. The results suggest that cord blood stem cells are beneficial in reversing the behavioral effects of spinal cord injury, even when infused 5 days after injury. Human cord blood-derived cells were observed in injured areas, but not in noninjured areas, of rat spinal cords, and were never seen in corresponding areas of spinal cord of noninjured animals. The results are consistent with the hypothesis that cord blood-derived stem cells migrate to and participate in the healing of neurological defects caused by traumatic assault. Center for Aging and Brain Repair and Department of Anatomy, University of South Florida College of Medicine, Tampa, FL 33612, USA. ssaporta@hsc.usf.edu http://www.ncbi.nlm.nih.gov/entrez/q..._uids=12857368
    • Kuh SU, Cho YE, Yoon DH, Kim KN and Ha Y (2005). Functional recovery after human umbilical cord blood cells transplantation with brain-derived neutrophic factor into the spinal cord injured rat. Acta Neurochir (Wien) 147: 985-92. There have been many efforts to recover neuronal function from spinal cord injuries, but there are some limitations in the treatment of spinal cord injuries.The neural stem cell has been noted for its pluripotency to differentiate into various neural cell types. The human umbilical cord blood cells (HUCBs) are more pluripotent and genetically flexible than bone marrow neural stem cells. The HUCBs could be more frequently used for spinal cord injury treatment in the future.Moderate degree spinal cord injured rats were classified into 3 subgroups, group A: media was injected into the cord injury site, group B: HUCBs were transplanted into the cord injury site, and group C: HUCBs with BDNF (Brain-derived neutrophic factor) were transplanted into the cord injury site. We checked the BBB scores to evaluate the functional recovery in each group at 8 weeks after transplantation. We then, finally checked the neural cell differentiation with double immunofluorescence staining, and we also analyzed the axonal regeneration with retrograde labelling of brain stem neurons by using fluorogold. The HUCBs transplanted group improved, more than the control group at every week after transplantation, and also, the BDNF enabled an improvement of the BBB locomotion scores since the 1 week after its application (P<0.05). 8 weeks after transplantation, the HUCBs with BDNF transplanted group had more greatly improved BBB scores, than the other groups (P<0.001). The transplanted HUCBs were differentiated into various neural cells, which were confirmed by double immunoflorescence staining of BrdU and GFAP & MAP-2 staining. The HUCBs and BDNF each have individual positive effects on axonal regeneration. The HUCBs can differentiate into neural cells and induce motor function improvement in the cord injured rat models. Especially, the BDNF has effectiveness for neurological function improvement due to axonal regeneration in the early cord injury stage. Thus the HUCBs and BDNF have recovery effects of a moderate degree for cord injured rats. Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea. http://www.ncbi.nlm.nih.gov/entrez/q..._uids=16010451
    Last edited by Wise Young; 04-07-2006 at 05:57 PM.

  5. #5

    Copying and Pasting studies

    In plain english are there any studies that have made rats walk with spinal cord injury? Sometimes, studies are used to make us think something significant has happened. Studies, with strange sounding Doctor names make you think this is important and cutting edge. It is like pharmaceuticals coming up with exotic names for the basic aspirin and people think it's something new and better. Are their any UCB studies that have made rats with sci walk?
    Last edited by howboutdis; 04-07-2006 at 07:07 PM.

  6. #6
    Quote Originally Posted by howboutdis
    In plain english are there any studies that have made rats walk with spinal cord injury? Sometimes, studies are used to make us think something significant has happened. Studies, with strange sounding Doctor names make you think this is important and cutting edge. It is like pharmaceuticals coming up with exotic names for the basic aspirin and people think it's something new and better. Are their any UCB studies that have made rats with sci walk?
    howboutdis,

    If you don't learn medical terminology, you will be at the mercy of interpreters of medical reports. So, I suggest that you learn the terminology if you are really interested.

    By the way, I did summarize the studies, in as plain English as I can. Yes, indeed, the studies do suggest that something important has happened. They report that umbilical cord blood cells have been transplanted into the spinal cord of rats, that the rats showed better walking scores. Unfortunately, the models of spinal cord injury used in many of the studies were hemisections (cutting half of the spinal cords). Most rats should recover walking within 2-3 weeks after a hemisection. It would have been more impressive if they had used a standardized spinal cord injury model such as a contusion. Nevertheless, they reported significant improvements of walking that are as significant as what Keirstead reported in his animals. Keirstead's study was better in that he used the contusion model. That is why the umbilical cord blood studies need to be confirmed with the contusion model and why we are taking the time to do them now.

    Wise.

  7. #7
    Banned Faye's Avatar
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    Quote Originally Posted by Wise Young
    Keirstead's study was better in that he used the contusion model. That is why the umbilical cord blood studies need to be confirmed with the contusion model and why we are taking the time to do them now.

    Wise.
    Thank you.

    It is good that you are trying to see if UCB stem cells can restore the ability to walk after SCI in rats. I'm also glad you agree that we haven't gotten to the point of being able to produce a video showing restored walking after UCB treatment yet in the rats.

    Though the behavior( migration and viability) of the transplanted cells is indeed interesting, and there is no doubt that some neurological improvement occurs, it still remains to be seen if walking ability can be sufficiently restored in rats using UCB stem cell treatments after SCI.

    Thank you also for quoting the stroke studies, though I generally ignore info on hemispheric strokes ( Occlusion of MCA ), for some of the same reasons you express reservations about results with hemisection models of SCI.

    "There’s far too much unthinking respect given to authority,” Molly Ivins explained; “What you need is sustained outrage.”
    Kerr, Keirstead, McDonald, Stice and Jun Yan courageously work on ESCR to Cure SCI.

    Divisiveness comes from not following Christopher Reeve's ESCR lead.
    Young does ASCR.
    [I]I do not tear down CRPA, I ONLY make peopl

  8. #8
    Faye,

    I think that you are mistakened to ignore MCAo treatment studies. I also think that you are wrong to rely on news reports and videos of selected animals, instead of the scientific reports themselves. Are you aware, by the way, that the walking rat videos shown on 60 minutes show about Dr. Keirstead are not from Dr. Keirstead? See http://carecure.org/forum/showthread.php?t=59477

    Wise.


    Quote Originally Posted by Faye
    Thank you.

    It is good that you are trying to see if UCB stem cells can restore the ability to walk after SCI in rats. I'm also glad you agree that we haven't gotten to the point of being able to produce a video showing restored walking after UCB treatment yet in the rats.

    Though the behavior( migration and viability) of the transplanted cells is indeed interesting, and there is no doubt that some neurological improvement occurs, it still remains to be seen if walking ability can be sufficiently restored in rats using UCB stem cell treatments after SCI.

    Thank you also for quoting the stroke studies, though I generally ignore info on hemispheric strokes ( Occlusion of MCA ), for some of the same reasons you express reservations about results with hemisection models of SCI.
    Last edited by Wise Young; 04-08-2006 at 07:51 AM.

  9. #9
    Dr. young,
    hi, i have a question. what is the chance of rejection of umbilical stem cells by the body when you use umbilical stem cells to repair spinal cord injury (since it is not from our own bodies) ? and if there is a chance of rejection, does that mean that we have to take anti rejection medications for the rest of our life? or there is a better solution to deal with rejection issue? thanks indeed.
    kz

  10. #10
    Quote Originally Posted by kz
    Dr. young,
    hi, i have a question. what is the chance of rejection of umbilical stem cells by the body when you use umbilical stem cells to repair spinal cord injury (since it is not from our own bodies) ? and if there is a chance of rejection, does that mean that we have to take anti rejection medications for the rest of our life? or there is a better solution to deal with rejection issue? thanks indeed.
    kz
    kz, good question. At the present, there are three potential sources of immune-compatible cells for transplantation.

    The first is autologous bone marrow. These are of course your own cells and should be immune compatible. There are of course many cells in bone marrow and the stem cells must be collected, identified, isolated, and purified. A number of companies are working on procedures to collect and purify these cells but unfortunately, there are no single marker for such cells. If one has a central laboratory to do this identication, isolation, and purification of the cells, the cells must be shipped to such a facility, processed, and then shipped back to the hospital for transplantation into the patient.

    The second is umbilical cord blood cells. These cells are collected at birth and then stored in cord blood banks. Of course, if the cells came from the baby that was born, the cells would be a perfect match. However, 99% of the people in the world don't have their own umbilical cord blood stored in some bank. Much experience, however, suggest that umbilical cord blood is transplants are well-tolerated by the immune system and that one can get 80% engraftment rates with only 4/6 HLA antigen matches. There are currently about 100,000 umbilical cord blood units stored around the world that are available for transplantation. Approximately 10% of these units will be matched in any given year, allowing 6,000-10,000 transplants a year. There is a bill in Congress and bills in various states (including New Jersey) to increase umbilical cord blood collection. But these are likely to increase the collection to perhaps 200,000.

    The third is heterologous HLA-antigen matched bone marrow cells. Millions of people have signed up for bone marrow donation programs. If a person requires a bone marrow stem cell transplant, their doctors will search through the databases from such transplants amongst the registrants. The chances of a match is less than 50%.

    There is controversy concerning what are the stem cells in bone marrow and umbilical cord blood. While several groups claim that they have the procedures to isolate the stem cells, none have really proven their case by showing that the cells isolated by their procedure works in humans. The proof is in the pudding and none have baked the pudding yet.

    For a while, Woo-Suk Hwang's claim to have been able to clone embryonic stem cells with nearly the same efficiency as in vitro fertilization gave everybody pause. That could have trumped the field. But, it turned out that he faked the results. Incidentally, the real issue is not whether it is possible to clone human embryonic stem cells (everybody that I know believes that it can and will happen) but whether it will be sufficiently efficient and cost-effective to compete with the headlong rush to develop non-immunogenic cells for transplantation.

    In our clinical trial of human umbilical cord blood transplants to the spinal cord, we are planning to use HLA-matched cells. This provides the best chance for the cells to survive in the spinal cord for the long term. We seriously considered the possibility of using bone marrow stem cells but ruled it out, at least for the present, because of the expense. We would need to invest in as much as $20 million into local GMP facilities to collect and process the cells, as well as a central GMP facility, to isolate and purify the cells. Not all the protocols have been developed and this is what we are working hard to accomplish.

    By the way, it is likely that this whole immunogenicity issue will be moot in the next 3-4 years. There is already some evidence indicating that it is possible to "immune-tolerize" people against specific cells. In other words, rather than finding a cell that matches the person's immune system, why not get the immune system to be tolerant to the cells being transplanted. We are working on this. The other reason is that we are very likely to be able to make any cell of the body into a stem cell. After all, a stem cell is only a cell that are expressing certain genes. Many of these genes have been identified and it is just a matter of time that somebody will figure out how to convert any cell into a stem cell.

    I am so saddened by the fact that our science policies are being determined by President Bush who is not only ignorant about science but makes decisions based on bad information and data. Throughout history, there have been Luddites or others who oppose advances in science. It took over 200 years for vaccination to become accepted. It took only 10 years or antibotics to be accepted, less than 10 years for in vitro fertilization to take place. In the end, the people will decide.

    Wise.

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