Spinal Cord Injury

Spinal Cord Injury Program

Spinal cord injury (SCI) is a devastating condition that impacts young and all people alike. SCI is complex and multifaceted with three major obstacles to therapy: loss of neurons, production of an impenetrable glial scar and loss of key insulating cells called oligodendrocytes. Stem cells overcome these problems to carry out repair and regeneration in many animals but in mammals like mice or humans resident stem cells are inhibited and remain dormant after injury. Researchers have found that injecting new stem cells into injured spinal cord produces remarkable results allowing paralyzed mice to walk again.  Beyond such replacement therapy, it is possible to activate the dormant, resident stem cells within the spinal cord to stimulate natural repair.  NSCI research has shown that small biodegradable beads that release stem cell activating factor stimulates resident stem cells to mediate repair and regeneration, and reverse paralysis. Stembeads are a novel bioengineered method to reawaken endogenous stem cells from dormancy and instruct them to promote repair and regeneration. NSCI is poised to move this exciting finding from laboratory mice to the bedside.

Retinitis Pigmentosa

Retinitis Pigmentosa Program

Retinitis PigmentosaThe Neural Stem Cell Institute and its parent non-profit the Regenerative Research Foundation, are committed to developing regenerative therapies for nervous system repair. We have a strong program focused on Retinitis Pigmentosa (RP), an important blinding disease for which current therapy is generally ineffective.  The basis of our RP program is the discovery of a unique adult human retinal pigment epithelium stem cell (RPESC) that can be extracted from patients up to age 99 years of age, thereby providing a patient-matched cell for transplantation therapy and for screening drugs effective against RP. This basic research program received competitive peer-review funding from the New York State Stem Cell Research Board, the American Health Assistance Foundation and the Steinbach Foundation. Having discovered this novel stem cell, we are now using the RPESC to benefit RP patients in translational research.

RP is a complex disease in which loss of retinal pigment epithelial cells (RPE) causes loss of the overlying neural retina and diminished vision. Human RPESCs can be used for cell replacement therapy to restore supportive RPE cell functions, improve retinal viability and preserve vision. Promising results using other types of stem cell for replacement therapy of RP are limited by immune rejection of the implanted foreign cells. This immune problem can be overcome because RPESC enable autologous transplantation. In this approach, RPESC are taken from a patient, expanded in culture and then replaced in the same patient. Before this can be offered to patients, however, we need to investigate the effect of RPESC cells implanted into animal models of RP to determine if RPESC, like other types of stem cells, improve vision. Another exciting line of research made possible by RPESC is to create disease models of RP in the culture dish, models that can be used to find drugs that slow RP progression. These are defined and critical projects that we are poised to accomplish, and we ask you to help fund this important work.

The NSCI is the first independent stem cell research institute in the USA. This not-for-profit 501c3 organization was co-founded by Sally Temple, Ph.D. who helped discover and define nervous system stem cells and who has recruited highly talented scientists working to translate discovery research into new therapies for central nervous system repair, and Jeffrey Stern, Ph.D., M.D., a physician-scientist who carries out research and cares for patients with retinal problems. At NSCI, our staff of 30 highly talented researchers work in a state of the art facility to translate discovery research into therapy for central nervous system repair. We are uniquely positioned to make headway in this exciting research, and your gift will enable us to take the defined steps needed to generate greatly needed novel therapeutics.

Parkinson’s Disease Program

Neural Stem Cell Institute researchers, and its parent non-profit organization the Regenerative Research Foundation, are discovering new ways to improve nerve repair.  We have recently recruited investigators working at the forefront of Parkinson’s Disease (PD) research, bringing their expertise to NSCI. With initial competitive funding from the New York State stem cell program (NYSTEM) we have already made exciting progress. Specifically, we have developed a new technique to generate human dopamine neurons (the cells that die in PD) from stem cells in large number.  This enables us to move forward on two important fronts – first the supply of stable, healthy neurons for development of cell replacement therapies in PD patients  and second, the production of mass quantities of cells that can be used to screen libraries of drugs to find therapeutics that slow or prevent PD progressing.

In PD, a very specific set of cells in the brain called dopamine neurons die.  These cells are responsible for regulating our movement.  As these neurons die, patients start to have difficulty walking and eventually can become immobile.  PD affects approximately 0.5 – 1 million patients in the US alone and current therapeutic strategies in PD are limited.  We still know relatively little about the disease, for example why these specific cells are dying, and because of this, drugs cannot be made properly. Pharmaceutical companies have libraries of compounds that could be useful, if we can create a drug screen that is highly relevant to PD. Our latest research has shown that we can successfully generate these human dopamine neurons in large numbers, sufficient for these cell-intensive drug screens. Now it is important that we test whether we can use these normal cells in two ways. First we will perform animal testing to determine whether these human dopaminergic neurons will be suitable for cell replacement therapies. Second, we will use them to create a disease model to mimic PD in the culture dish, allowing clinical drug studies to seek compounds that prevent their death.

The NSCI is the first independent neural stem cell research institute in the USA. It was co-founded by Sally Temple, a scientist who helped discover and define nervous system stem cells. She has recruited highly talented individuals to work on translating discovery research to find new therapies for central nervous system repair. The Institute is a state of the art facility with first rate investigators and staff who are hard-working and dedicated to finding solutions to these pressing health problems. The multiple programs that  NSCI runs allows valuable cross-pollination. Our collaborations with researchers at major academic centers around the world allows us to take advantage of the latest technology and research findings, focusing these on central nervous system regenerative therapies. We are uniquely positioned to make headway in this exciting research environment, and your gift will enable us to take the defined steps needed towards novel therapeutics.

Optic Neuropathy Program

Vision loss from optic nerve injury due to trauma, multiple sclerosis or vascular disorders such as NAION is complex and multifaceted. Successful treatment of this devastating condition is limited by three major challenges:  loss of neurons, production of an impenetrable glial scar and loss of key supporting cells called oligodendrocytes. Stem cells present in the optic nerve of many animals overcome these problems to carry out repair and regeneration but in mammals like mice or humans these CNS stem cells are inhibited and remain dormant after injury.  Injecting stem cells into damaged spinal nerve tracts that closely resemble the optic nerve improves function in mice and some groups have injected stem cells to treat spinal cord injury in man. These studies raise hope that stem cell replacement therapy can be employed to treat damaged optic nerve.

Beyond replacement therapy, a unique approach taken at the Neural Stem Cell Institute (NSCI) is to stimulate the endogenous stem cells naturally present but dormant within the optic nerve. Activating such endogenous stem cells by implantation of biodegradable beads that release stem cell activating growth factor addresses all three problems limiting treatment and dramatically improves function in mice with injured spinal nerve tracts that mirror optic nerve injury.  The discovery of Stembeads offers a novel bioengineered method to activate endogenous stem and progenitor cells, reawakening them from dormancy and instructing them to promote repair and regeneration. NSCI is poised to accomplish the defined and critical next step treating the optic nerve directly to translate the Steambead discovery into beneficial therapy.

Macular Degeneration Program

Macular DegenerationAMD is the leading cause of vision loss in the USA. This devastating condition begins when abnormal deposits called drusen form under the retinal pigment epithelium (RPE) in the macular region of the retina. Drusen disrupt RPE cells and weaken the overlying retina to cause diminished vision. Stem cell research can benefit AMD patients in two ways. New RPE cells can be made from embryonic stem cells (ESC) and then injected under the retina to replace damaged RPE. This stem cell based replacement therapy restores vision in animal models of AMD.  Our work at NSCI aims to determine the optimal type of stem cell for replacement of damaged RPE. We have discovered a unique, human RPE stem cell (RPESC) and are working to ascertain that the RPESC is a safe and effective stem cell for replacement therapy of AMD.

Stem cells are also used for drug discovery.  The healthy RPE made for replacement therapy can be stressed to produce abnormal cells that display features of AMD. Recreating key characteristics of AMD in cells in the culture dish greatly accelerates screening for drugs using high throughput stem cell-based AMD models. The RPESC discovered at NSCI is uniquely suitable for creating such AMD models and screening tests to discover new AMD drugs is underway.

Further reading:

Retinal Repair by Stem Cell Transplantation 2006 Jeffrey Stern, Sally Temple and Soma De in Stem Cell Frontiers in Regenerative Medicine and Gene-based Therapy edited by Alexander Battler and Jonathan Leor, Springer-London.

Brain Injury and Stroke Program

Brain injury is a devastating condition associated with trauma, multiple sclerosis or stroke.  Successful therapy must overcome the associated loss of neurons and supporting glial cells as well as complex intercellular connections. This daunting challenge can be addressed using stem cells that originated in the brain and have the capacity to regenerate and repair this delicate tissue. Brain stem cells remain dormant after injury in higher species like mice or man but do mediate regeneration and repair in lower animals. If this inhibition of stem cells can be overcome then brain regeneration and repair can become a reality.

New stem cells injected into injured brain overcome inhibition to reproduce and integrate into injured brain tissues. Embryonic stem cells can proliferate too much, however, and sometimes make the wrong progeny while more differentiated neural stem cells generate appropriate progeny but may not proliferate or integrate sufficiently for meaningful recovery. The remaining challenge is to find the stem cells most suited to a particular injury. The ideal stem cell is the type already resident in the brain. These dormant brain stem cells can be activated by implantation of biodegradable beads that release stem cell activating factor. Activation of endogenous stem cells has the power to repair spinal cord injuries that mirror brain injury. This new therapeutic approach to nervous system repair, Stembeads, is a novel bioengineered method to reawaken dormant stem cells and direct natural regeneration and repair of damaged brain. The defined steps needed to translate this exciting finding from the laboratory to the patient’s bedside are within reach.

Stem Cell Publications

Publications

Fasano C.A,, Chambers SM, Lee G, Tomishima MJ, and Studer L. (2010) Efficient derivation of floor plate tissue from human embryonic stem cells.  Cell Stem Cell, 6(4):336-347.

Phoenix TN, Temple S.(2010) Spred1, a negative regulator of Ras-MAPK-ERK, is enriched in CNS germinal zones, dampens NSC proliferation, and maintains ventricular zone structure.
Genes Dev. 1;24(1):45-56.
Fasano, C.A., Studer, L. (2009) Too much Sonic, too little neurons. Nature Neuroscience, 12(2): 1007-8

Fasano C.A, Phoenix TN, Kokovay E, Lowry N, Elkabetz Y, Dimos JT, Lemischka IR, Studer L, Temple S. (2009) Bmi-1 cooperates with Foxg1 to maintain neural stem cell self-renewal in the forebrain. Genes Dev 23:561-74

Chambers, S.M., Fasano, C.A., Papapetrou, E.P., Tomishima, M., Sadelain, M., and Studer, L. (2009) Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nature Biotechnology, (3) 275-80.

Lee, G, Papapetrou, E. P., Kim, H., Chambers, S.M., Tomishima, M., Fasano, C.A., Viale, A., Tabar, V., Sadelain, M., and Studer, L. (2009) Modeling Pathogenesis and Treatment of Familial Dysautonomia in Patient Specific Pluripotent Stem Cells.  Nature, Sep 17;461(7262):402-6.

Fasano C.A, Phoenix TN, Kokovay E, Lowry N, Elkabetz Y, Dimos JT, Lemischka IR, Studer L, Temple S. (2009) Bmi-1 cooperates with Foxg1 to maintain neural stem cell self-renewal in the forebrain. Genes Dev 23:561-74

Corneo BTemple S. (2009) Sense and serendipity aid RPE generation.Cell Stem Cell. Oct 2;5(4):347-8.

Phoenix TN, Temple S (2009)Baby got brain: Fgf10 sets rostral cortical size..Neuron. Jul 16;63(1):1-3.

Cohen AR, Bjornsson CS, Temple S, Banker G, Roysam B.(2009) Automatic summarization of changes in biological image sequences using algorithmic information theory. IEEE Trans Pattern Anal Mach Intell. Aug;31(8):1386-403.

Okano H, Temple S. (2009) Cell types to order: temporal specification of CNS stem cells Curr Opin Neurobiol.  Apr;19(2):112-9. Epub 2009 May 6. Review

Shen Q, Temple S. (2009) Fine control: microRNA regulation of adult neurogenesis. Nature Neuroscience 12:369-70

Lowry NA, Temple S. (2009) Identifying the perpetrator in medulloblastoma: Dorian Gray versus Benjamin Button. Cancer Cell 15:83-5.

Kokovay E, Shen Q, Temple S. (2008) The incredible elastic brain: how neural stem cells expand our minds. Neuron 60:420-9.

SlaterJL, Landman KA, Hughes BD, Shen Q Temple S. (2009) Cell lineage tree models of neurogenesis. J Theor Biol 256: 164-79.

Shen Q, Wang Y, Kokovay E, Lin G, Chuang SM, Goderie SK, Roysam B, Temple S. (2008) Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions.  Cell Stem Cell 3:289-300.

Lowry N, Goderie SK, Adamo M, Lederman P, Charniga C, Gill J, Silver J, Temple S. (2008) Multipotent embryonic spinal cord stem cells expanded by endothelial factors and Shh/RA promote functional recovery after spinal cord injury. Exp Neurol. 209:510-22.

Kokovay E, Temple S (2007) Taking neural crest stem cells to new heights. Cell 131:234-6

Ashton RS, Peltier J, Fasano CA, O’Neill A, Leonard J, Temple S, Schaffer DV, Kane R. (2007) High-Throughput Screening of Gene Function in Stem Cells using Clonal Microarrays.  Stem Cells. 25:2928-35.

Fasano CA, Dimos JT, Ivanova NB, Lemischka IR, Temple, S (2007) shRNA knockdown of Bmi-1 reveals a critical role for p21/Rb pathway in NSC self-renewal during development. Cell Stem Cell 1:87-99.

De S., Rabin D.; Salero E; Lederman PL; Temple S, Stern, JH (2007) Human RPE cells change to express B-crystallin: A Biomarker for RPE-cell change in Age-Related Macular Degeneration. Archives of Ophthalmology 125: 641-5

Salero E and Hatten ME (2007) Differentiation of ES Cells into Cerebellar Neurons. Proc Natl. Acad. Sci. 20: 104(8):2997-3002.

Lowry NATemple S (2007) Making Human Neurons from Stem Cells after Spinal Cord Injury  PLoS Med. 4:e48

Corneo B, Wendland RL, Deriano L, Cui X, Klein IA, Wong SY, Arnal S, Holub AJ, Weller GR, Pancake BA, Shah S, Brandt VL, Meek K, Roth DB. (2007). Rag mutations reveal robust alternative end joining.  Nature 449(7161):483-6.

Shen Q, Wang J, Dimos JT, Fasano CA, Phoenix TN, Lemischka IR, Ivanova NB,  Stifani S, Morrisey EE, Temple S (2006) The timing of cortical neurogenesis is encoded within lineages of individual progenitor cells. Nature Neuroscience 9:743-51.

Pumiglia K, Temple S.( 2006) PEDF: bridging neurovascular interactions in the stem cell niche. Nature Neuroscience. 9:299-300.

Al-Kofahi O, Radke RJ, Goderie SK, Shen Q, Temple S, Roysam B. (2006) Automated cell lineage construction: a rapid method to analyze clonal development established with murine neural progenitor cells. Cell Cycle  5:327-35.

Stern JH, Temple, S, De S.  (2006) Retinal Repair by Stem Cell Transplantation.  Chapter in: Stem Cell and Gene Based Therapy: Frontiers in Regenerative Medicine, editors Battler A. and Leor J, Springer-Verlag, pp. 259-80.

Capela A, Temple S. (2006) LeX carbohydrate expression by progenitor cells with high growth and neurogenic potential in the embryonic nervous system. Developmental Biology  291:300-13.

Natalia Abramova, Carol Charniga, Susan K. Goderie, Sally Temple (2005) Stage-specific changes in gene expression in acutely isolated mouse CNS progenitor cells. Developmental Biology 283:269-281.

Yu Sun, Goderie Susan K., Temple S. (2005) Asymmetric distribution of EGF receptor during mitosis generates diverse CNS progenitor cells. Neuron 45:873-886.

Shen, Q., Goderie, S., Jin, L., Karanth, N., Sun, Y., Abramova, N., Vincent, P., Pumiglia,K., Temple, S. (2004) Endothelial Cells Stimulate Self-Renewal and Expand Neurogenesis of Neural Stem Cells. Science 304:1338-1340

Li HS, Wang D, Shen Q, Schonemann MD, Gorski JA, Jones KR, Temple S, Jan LY,
Jan YN. (2003). Inactivation of Numb and Numblike in embryonic dorsal forebrain impairs neurogenesis and disrupts cortical morphogenesis. Neuron 40:1105-18.

Temple S. (2003) Embryonic stem cell self-renewal, analyzed. Cell 115:247-8.

Salero E, Gimenez C, Zafra F (2003) Identification of a non-canonical E-box motif as a regulatory element in the proximal promoter region of apolipoprotein E gene. Biochem J 370: 979-86.

Shen Q, Temple S.  (2002). Creating asymmetric cell divisions by skewing endocytosis.  Review Science STKE 162:PE52.

Schneider AS, Atluri P, Shen Q, Barnes W, Mah SJ, Stadfelt D, Goderie SK, Temple S, Fleck MW. (2002)  Functional nicotinic acetylcholine receptor expression on stem and progenitor cells of the early embryonic nervous system. Ann N Y Acad Sci. 971:135-8.

Capela A, Temple S. (2002). LeX/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal. Neuron 35:865-75.

Shen Q, Zhong W, Jan YN, Temple S. (2002).  Asymmetric Numb distribution is critical for asymmetric cell division of mouse cerebral cortical stem cells and neuroblasts. Development 129:4843-53.

Corneo B, Benmerah A, Villartay JP. (2002). A short peptide at the C terminus is responsible for the nuclear localization of RAG2. Eur J Immunol. 32:2068-73.

Temple S. (2001) The development of neural stem cells. Nature 414: 112-118.

He W., Ingraham C., Rising L., Goderie S., Temple S. (2001) Multipotent stem cells from the mouse basal forebrain contribute GABAergic neurons and oligodendrocytes to the cerebral cortex during embryogenesis. J. Neurosci. 21: 8854-62

Atluri P, Fleck MW, Shen Q, Mah SJ, Stadfelt D, Barnes W, Goderie SK, Temple S, Schneider AS (2001). Functional nicotinic acetylcholine receptor expression in stem and progenitor cells of the early embryonic mouse cerebral cortex. Dev Biol. 240:143-56.

Temple S. (2001) Stem cell plasticity—Building the brain of our dreams. Nat Rev Neurosci. 2:513-20.

Temple, S.  (2001) Defining neural stem cells and their role in normal development of the nervous system.  Chapter in: Neural stem cells, ed. M. Rao, Humana Press.

Salero E, Perez Sen R, Aruga J, Gimenez C and Zafra F (2001) Transcription factors Zic1 and Zic2 bind and transactive the apolipoprotein E gene promoter. J Biol Chem 276: 3 18881-8.

Yan J, Studer L, McKay RD. J  (2001) Ascorbic acid increases the yield of dopaminergic neurons derived from basic fibroblast growth factor expanded mesencephalic precursors. Neurochem. Jan;76(1):307-11.

Moshous D., Callebaut I., de Chasseval R., Corneo B., Cavazzana-Calvo M., Le Deist F., Tezcan I., Sanal O., Bertrand Y., Philippe N., Fischer A. and de Villartay J.P. (2001) Artemis, a novel DNA double strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency.  Cell 105: (177-186).

Corneo B., Moshous D., Güngor T., Wulffraat  N., Philippet  P., Le Deist F., Fischer  A., and de Villartay J.P. (2001) Identical mutations in RAG1 or RAG2 genes leading to defective V(D)J recombinase activity can cause either T-B-SCID or Omenn syndrome. Blood  97 (9) : 2772-2776.

Qian, X., Shen, Q., Goderie, S.K., He, Wenlei, Capela, A. and Temple, S. (2000) Timing of CNS cell generation: a programmed sequence of neron and glial cell production from islated murine cortical stem cells Neuron 28: 69-80.

Corneo B., Moshous D., Callebaut I., de Chasseval R., Fischer A., de Villartay J.P.  (2000) Three-dimensional clustering of human Rag2 gene mutations in severe combined immunodeficiency. J. Biol . Chem. 275 (17) :12672-12675.

Temple, S. (1999) CNS development: The obscure origins of the adult stem cells.  Review, Current Biol., 9:R397-9.

Temple, S. and Alvarez- Buylla, A. (1999) Stem cells in the adult mammalian central nervous system. Review, Curr. Opin. Neurobiol. 9:135-41.

Shen, Q., Qian, X., Capela, A. and Temple, S (1998). Stem cells in the embryonic cerebral cortex – their role in histogenesis and patterning.  Review, J. Neurobiol. 36: 162-174.

Yan J and  Barrett JN Purification from bovine serum of a survival-promoting factor for cultured central neurons and its identification as selenoprotein P. J Neurosci. 1998 Nov 1;18(21):8682-91.

Alvarez-Buylla, A. and Temple, S. (1998) Stem cells in the developing and adult nervous system.  J. Neurobiol. 36: 105-110.

Qian, X., Goderie, S.K., Shen, Q., Stern, J.H. and Temple, S. (1998) Intrinsic Programs of Patterned Cell Lineages in Isolated Vertebrate CNS Ventricular Zone Cells, Development 125: 3143-3152.

Qian, X., Davis A.A., Goderie, S.K. and Temple, S. (1997).  FGF2 concentration regulates the generation of neurons and glia from multipotent cortical stem cells.   Neuron 18: 81-93.

Strazzabosco M., Corneo B., Iemmolo R.M., Menin C., Gerunda G., Bonaldi L., Merenda R., Neri D., Poletti A., Montagna M., Del Mistro A., Maffei Faccioli A., D’Andrea E. (1997) Epstein-Barr virus-associated post-transplant lympho-proliferative disease of donor origin in liver transplant recipients. J. Hepatol. 26 (4) : 926-934.

Temple, S. (1996) Out of the shadows.  Book review, Nature 381.

Temple, S. and Qian, X. (1996) Vertebrate neural progenitor cells: sub-types and regulation Curr. Opinion in Neurobiol.  6: 11-17.

Lah TT, Calaf G, Kalman E, Shinde BG, Somer R, Estrada S, Salero E, Russo J and Daskal I (1996) Capthepsins D, B and L in transformed human breast epithelial cells. Breast Cancer Res Treat 39: 2 221-233.

Montagna M., Santacatterina M., Corneo B., Menin C., Serova O., Lenoir G.M., Chieco-Bianchi L., D’Andrea E. (1996) Identification of seven new BRCA1 germline mutations in Italian breast and breast-ovarian cancer families. Cancer Res., 56 (23) : 5466-5469.

Menin C., Indraccolo S., Montagna M., Corneo B., Bonaldi L., Leib-Mosch C., Chieco-Bianchi L., D’Andrea E. (1996). Identification of a human endogenous LTR-like sequence using HIV-I LTR specific primers. Molec. Cell.Probes, 10 (6) : 443-451.

Temple, S. and Qian, X.  (1995)  bFGF, Neurotrophins and the Control of cortical Neurogenesis. Neuron 15: 249-252.

Salero E, Vergara, P and Segovia, J (1995) Intracellular increases of cAMP induce opposite effects in glutamic acid descarboxilase (GAD67) and glial fibrillary acidic protein immunoreactivities in C6 cells. Neurosci Lett 191: 1-2 9-12.

Menin C., Ometto L., Veronesi A., Coppola V., Veronese M. L., Indraccolo S., Bruni L., Corneo B., Amadori A., De Rossi A., Chieco-Bianchi L., D’Andrea E. (1995). Dominance of a single Epstein-Barr virus strain in SCID mouse tumors induced by injection of peripheral blood mononuclear cells from healthy human donors. Virus Res., 36 (2-3): 215-231.

Davis, A.A. and Temple, S. (1994) A self-renewing, multipotential stem cell in embryonic rat cerebral cortex.   Nature 372: 263-266.

Temple, S. and Davis, A.A. (1994)   Isolated rat cortical progenitor cells are maintained in division in vitro by membrane-associated factors.  Development 120:999.

Nonner, D, Temple S. and Barrett J.N. (1992) Rat embryonic septal neurons survive and express cholinergic properties in isolation and without nerve growth factor.  Develop Brain Res. 70,197-205.

Temple, S. (1990) Characteristics of cells that give rise to the central nervous system.  Review, J. of Cell Science 97: 213-219.

Temple S. (1989) Division and differentiation of isolated CNS blast cells in microculture.  Nature 340:471-473.

Raff, M.C., Temple,S. and ffrench-Constant,C. (1987)  Glial cell development and function in the rat optic nerve. Prog. In Brain Res. 71:435-438.

Temple, S. and Raff, M.C. (1986) Clonal analysis of oligodendrocyte development in culture: Evidence for a developmental clock that counts cell divisions. Cell 44:773-779.

Temple, S. (1986) Single cell studies of optic nerve development. PhD dissertation, University College London, England.

Temple, S. and Raff, M.C. (1985) Differentiation of a bipotential progenitor cell in single cell microculture.  Nature 313:223-225.