UHealth - University of Miami Health System

Jacqueline Sagen, Ph.D., M.B.A.

General Information

Jacqueline  Sagen, Ph.D., M.B.A.

Contact

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Languages

  • English

Roles

  • Professor

Research Interests

The field of neural transplantation has witnessed resurgence due to the potential for cellular implants to provide therapeutic benefits and restore function in the nervous system. Cells implanted into the central nervous system (CNS) can be utilized in several ways: 1) as living cellular minipumps, providing a continually renewable supply of naturally derived therapeutic molecules such as neurotransmitters or trophic factors; 2) as supportive matrices or bridges for axonal regrowth; 3) as replacement of lost neuronal populations consequent to neurological injury or disease. Our laboratory uses all of these neural transplantation strategies in order to explore more promising approaches in the treatment of debilitating CNS disorders.

Particularly amenable to the minipump approach are chronic pain syndromes, which require long-term therapeutic management. Research in my laboratory has indicated that cellular implants in the spinal subarachnoid space can alleviate many symptoms of chronic pain in animal models. For these studies, chromaffin cells from the adrenal medulla have been utilized as a graft source because these cells produce a cocktail of agents - including opioid peptides, catecholamines, endogenous NMDA antagonists, and trophic factors - which can reduce pain when administered directly into the spinal fluid. Results from animal studies have led to the initiation of clinical trials at several centers in patients with intractable pain, with encouraging results. However, before large-scale implementation, several issues need to be addressed, particularly the identification of more practical and improved sources of donor cells such as xenografts or engineered cell lines. This is a current focus of research in my laboratory. If successful, the findings from these studies could lead to novel therapies in the long-term management of chronic pain syndromes, particularly for patients refractory to traditional pharmacotherapies, who would benefit greatly by improved quality of life free from pain.

Another current research focus utilizes the cellular replacement approach in order to restore function following spinal cord and brain injury. An emergent breakthrough in recent years was the discovery that stem cells possessing the capacity to generate new neural cells and replace lost cellular populations exist in the CNS. Like stem cells identified in other biological systems, neural stem cells are capable of self-renewal, proliferation, and generation of a large number of progeny. In addition, these cells have the capacity to give rise to progenitor neural cell lineages appropriate for their location and metabolic circumstances when exposed to microenvironmental cues, and have been demonstrated to differentiate in vitro into the three major neural phenotypes: neurons, astrocytes, and oligodendrocytes. However, when transplanted to the adult CNS, neuronal differentiation is limited, possibly due to the lack of developmental cues present in the embryonic environment normally encountered by these cells. Thus, additional manipulations, such as exposure to trophic factors, genetic engineering, and/or cellular pre-differentiation will likely be necessary. Our laboratory is exploring the use of neural stem cell transplants for spinal cord injury, traumatic brain injury, and chronic pain. For each of these applications, unique strategies will be required for distinctive cellular populations. Our current strategies for neural stem cell transplantation in spinal cord injury include genetic premodification, co-grafting with trophic factor-producing cells, and combinations with axonal bridges in order to promote more complete restoration of spinal circuitry.

In summary, the overall aim of research in my laboratory is the utilization of neural transplants to restore quality of life and alleviate suffering from the most devastating of human disorders resulting from injury to the nervous system.

Publications
1: Raeder H, Johansson S, Holm PI, Haldorsen IS, Mas E, Sbarra V, Nermoen I, Eide SA, Grevle L, Bjorkhaug L, Sagen JV, Aksnes L, Sovik O, Lombardo D, Molven A, Njolstad PR.
Abstract Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction.
Nat Genet. 2006 Jan;38(1):54-62. Epub 2005 Dec 20.
PMID: 16369531 [PubMed - in process]

2: Bjorkhaug L, Johansson S, Raeder H, Thorsby PM, Undlien DE, Sovik O, Molven A, Sagen JV, Njolstad PR.
Free Full Text [Molecular diagnostics in diabetes mellitus]
Tidsskr Nor Laegeforen. 2005 Nov 3;125(21):2968-72. Review. Norwegian.
PMID: 16276383 [PubMed - indexed for MEDLINE]

3: Sagen JV, Baumann ME, Salvesen HB, Molven A, Sovik O, Njolstad PR.
Abstract Diagnostic screening of NEUROD1 (MODY6) in subjects with MODY or gestational diabetes mellitus.
Diabet Med. 2005 Aug;22(8):1012-5.
PMID: 16026366 [PubMed - indexed for MEDLINE]

4: NasiriNezhad F, Sagen J.
Abstract NMDA antagonist peptide supplementation enhances pain alleviation by adrenal medullary transplants.
Cell Transplant. 2005;14(4):203-11.
PMID: 15929555 [PubMed - indexed for MEDLINE]

5: Sagen JV, Pearson ER, Johansen A, Spyer G, Sovik O, Pedersen O, Njolstad PR, Hattersley AT, Hansen T.
Abstract Preserved insulin response to tolbutamide in hepatocyte nuclear factor-1alpha mutation carriers.
Diabet Med. 2005 Apr;22(4):406-9.
PMID: 15787664 [PubMed - indexed for MEDLINE]

6: Sagen JV, Raeder H, Hathout E, Shehadeh N, Gudmundsson K, Baevre H, Abuelo D, Phornphutkul C, Molnes J, Bell GI, Gloyn AL, Hattersley AT, Molven A, Sovik O, Njolstad PR.
Free Full Text Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy.
Diabetes. 2004 Oct;53(10):2713-8.
PMID: 15448106 [PubMed - indexed for MEDLINE]

7: Caban AJ, Hama AT, Lee JW, Sagen J.
Abstract Enhanced antinociception by nicotinic receptor agonist epibatidine and adrenal medullary transplants in the spinal subarachnoid space.
Neuropharmacology. 2004 Jul;47(1):106-16.
PMID: 15165838 [PubMed - indexed for MEDLINE]

8: Akbari M, Skjelbred C, Folling I, Sagen J, Krokan HE.
Abstract A gel electrophoresis method for detection of mitochondrial DNA mutation (3243 tRNA(Leu (UUR))) applied to a Norwegian family with diabetes mellitus and hearing loss.
Scand J Clin Lab Invest. 2004 Apr;64(2):86-92.
PMID: 15115244 [PubMed - indexed for MEDLINE]

9: Sagen J.
Free Full Text Cellular therapies for spinal cord injury: what will the FDA need to approve moving from the laboratory to the human?
J Rehabil Res Dev. 2003 Jul-Aug;40(4 Suppl 1):71-9. Review.
PMID: 15077651 [PubMed - indexed for MEDLINE]

10: Schumm MA, Castellanos DA, Frydel BR, Sagen J.
Abstract Improved neural progenitor cell survival when cografted with chromaffin cells in the rat striatum.
Exp Neurol. 2004 Jan;185(1):133-42.
PMID: 14697324 [PubMed - indexed for MEDLINE]

11: Schumm MA, Castellanos DA, Frydel BR, Sagen J.
Abstract Direct cell-cell contact required for neurotrophic effect of chromaffin cells on neural progenitor cells.
Brain Res Dev Brain Res. 2003 Dec 19;146(1-2):1-13.
PMID: 14643006 [PubMed - indexed for MEDLINE]

12: Njolstad PR, Sagen JV, Bjorkhaug L, Odili S, Shehadeh N, Bakry D, Sarici SU, Alpay F, Molnes J, Molven A, Sovik O, Matschinsky FM.
Free Full Text Permanent neonatal diabetes caused by glucokinase deficiency: inborn error of the glucose-insulin signaling pathway.
Diabetes. 2003 Nov;52(11):2854-60.
PMID: 14578306 [PubMed - indexed for MEDLINE]

13: Sagen JV, Bostad L, Njolstad PR, Sovik O.
Abstract Enlarged nephrons and severe nondiabetic nephropathy in hepatocyte nuclear factor-1beta (HNF-1beta) mutation carriers.
Kidney Int. 2003 Sep;64(3):793-800.
PMID: 12911528 [PubMed - indexed for MEDLINE]

14: Sovik O, Sagen J, Njolstad PR, Nyland H, Myhr KM.
No abstract Contributions to the MODY5 phenotype.
J Inherit Metab Dis. 2002 Nov;25(7):597-8. No abstract available.
PMID: 12638944 [PubMed - indexed for MEDLINE]

15: Bjorkhaug L, Sagen JV, Thorsby P, Sovik O, Molven A, Njolstad PR.
Free Full Text Hepatocyte nuclear factor-1 alpha gene mutations and diabetes in Norway.
J Clin Endocrinol Metab. 2003 Feb;88(2):920-31.
PMID: 12574234 [PubMed - indexed for MEDLINE]

16: Hama A, Woon Lee J, Sagen J.
Abstract Differential efficacy of intrathecal NMDA receptor antagonists on inflammatory mechanical and thermal hyperalgesia in rats.
Eur J Pharmacol. 2003 Jan 10;459(1):49-58.
PMID: 12505533 [PubMed - indexed for MEDLINE]

17: Bes JC, Sagen J.
No abstract Dissociated human embryonic and fetal adrenal glands in neural stem cell culture system: open fate for neuronal, nonneuronal, and chromaffin lineages?
Ann N Y Acad Sci. 2002 Oct;971:563-72. No abstract available.
PMID: 12438184 [PubMed - indexed for MEDLINE]

18: Schumm MA, Castellanos DA, Frydel BR, Sagen J.
Abstract Enhanced viability and neuronal differentiation of neural progenitors by chromaffin cell co-culture.
Brain Res Dev Brain Res. 2002 Aug 30;137(2):115-25.
PMID: 12220703 [PubMed - indexed for MEDLINE]

19: Sagen JV, Njolstad PR, Sovik O.
No abstract Reduced prevalence of late-diabetic complications in MODY3 with early diagnosis.
Diabet Med. 2002 Aug;19(8):697-8. No abstract available.
PMID: 12147154 [PubMed - indexed for MEDLINE]

20: Siegan JB, Herzberg U, Frydel BR, Sagen J.
Abstract Adrenal medullary transplants reduce formalin-evoked c-fos expression in the rat spinal cord.
Brain Res. 2002 Jul 19;944(1-2):174-83.
PMID: 12106677 [PubMed - indexed for MEDLINE]

21: Castellanos DA, Tsoulfas P, Frydel BR, Gajavelli S, Bes JC, Sagen J.
Abstract TrkC overexpression enhances survival and migration of neural stem cell transplants in the rat spinal cord.
Cell Transplant. 2002;11(3):297-307.
PMID: 12075995 [PubMed - indexed for MEDLINE]

22: Vizzardelli C, Potter ED, Berney T, Pileggi A, Inverardi L, Ricordi C, Sagen J.
Abstract Automated method for isolation of adrenal medullary chromaffin cells from neonatal porcine glands.
Cell Transplant. 2001;10(8):689-96.
PMID: 11814111 [PubMed - indexed for MEDLINE]

23: Hama A, Sagen J.
Abstract Selective antihyperalgesic effect of [Ser1] histogranin on complete Freund's adjuvant-induced hyperalgesia in rats.
Pain. 2002 Jan;95(1-2):15-21.
PMID: 11790463 [PubMed - indexed for MEDLINE]

24: Herzberg U, Sagen J.
Abstract Peripheral nerve exposure to HIV viral envelope protein gp120 induces neuropathic pain and spinal gliosis.
J Neuroimmunol. 2001 May 1;116(1):29-39.
PMID: 11311327 [PubMed - indexed for MEDLINE]

25: Hentall ID, Noga BR, Sagen J.
Free Full Text Spinal allografts of adrenal medulla block nociceptive facilitation in the dorsal horn.
J Neurophysiol. 2001 Apr;85(4):1788-92.
PMID: 11287501 [PubMed - indexed for MEDLINE]

26: Eaton MJ, Martinez M, Karmally S, Lopez T, Sagen J.
Abstract Initial characterization of the transplant of immortalized chromaffin cells for the attenuation of chronic neuropathic pain.
Cell Transplant. 2000 Sep-Oct;9(5):637-56.
PMID: 11144961 [PubMed - indexed for MEDLINE]

27: Hentall ID, Sagen J.
No abstract The alleviation of pain by cell transplantation.
Prog Brain Res. 2000;127:535-50. Review. No abstract available.
PMID: 11142047 [PubMed - indexed for MEDLINE]

28: Yadid G, Zangen A, Herzberg U, Nakash R, Sagen J.
Abstract Alterations in endogenous brain beta-endorphin release by adrenal medullary transplants in the spinal cord.
Neuropsychopharmacology. 2000 Dec;23(6):709-16.
PMID: 11063926 [PubMed - indexed for MEDLINE]

29: Eaton MJ, Frydel BR, Lopez TL, Nie XT, Huang J, McKillop J, Sagen J.
Abstract Generation and initial characterization of conditionally immortalized chromaffin cells.
J Cell Biochem. 2000 Jul 19;79(1):38-57.
PMID: 10906754 [PubMed - indexed for MEDLINE]

30: Lazorthes Y, Sagen J, Sallerin B, Tkaczuk J, Duplan H, Sol JC, Tafani M, Bes JC.
Abstract Human chromaffin cell graft into the CSF for cancer pain management: a prospective phase II clinical study.
Pain. 2000 Jul;87(1):19-32.
PMID: 10863042 [PubMed - indexed for MEDLINE]

31: Duplan H, Bes JC, Tafani M, Sallerin B, Sagen J, Ohayon E, Lazorthes Y, Tkaczuk J.
Abstract Adrenal medullary explants as an efficient tool for pain control: adhesive biomolecular components are involved in graft function ex vivo.
Exp Neurol. 2000 Jun;163(2):331-47.
PMID: 10833307 [PubMed - indexed for MEDLINE]

32: Hentall ID, Sagen J.
Abstract Spinal CSF from rats with painful peripheral neuropathy evokes catecholamine release from chromaffin cells in vitro.
Neurosci Lett. 2000 Jun 2;286(2):95-8.
PMID: 10825645 [PubMed - indexed for MEDLINE]

33: Hama AT, Siegan JB, Herzberg U, Sagen J.
Abstract NMDA-induced spinal hypersensitivity is reduced by naturally derived peptide analog [Ser1]histogranin.
Pharmacol Biochem Behav. 1999 Jan;62(1):67-74.
PMID: 9972847 [PubMed - indexed for MEDLINE]

34: Sovik O, Njolstad P, Folling I, Sagen J, Cockburn BN, Bell GI.
No abstract Hyperexcitability to sulphonylurea in MODY3.
Diabetologia. 1998 May;41(5):607-8. No abstract available.
PMID: 9628283 [PubMed - indexed for MEDLINE]

35: Njolstad PR, Sovik O, Bell GI, Cockburn BN, Folling I, Sagen J.
Abstract [Non-insulin dependent diabetes in children and adolescents]
Tidsskr Nor Laegeforen. 1998 Mar 10;118(7):1054-7. Norwegian.
PMID: 9531829 [PubMed - indexed for MEDLINE]

36: Siegan JB, Sagen J.
Abstract Adrenal medullary transplants attenuate sensorimotor dysfunction in rats with peripheral neuropathy.
Pharmacol Biochem Behav. 1998 Jan;59(1):97-104.
PMID: 9443542 [PubMed - indexed for MEDLINE]

37: Sagen J.
No abstract Cellular transplantation for intractable pain.
Adv Pharmacol. 1998;42:579-82. No abstract available.
PMID: 9327968 [PubMed - indexed for MEDLINE]

38: Czech KA, Ryan JW, Sagen J, Pappas GD.
Abstract The influence of xenotransplant immunogenicity and immunosuppression on host MHC expression in the rat CNS.
Exp Neurol. 1997 Sep;147(1):66-83.
PMID: 9294404 [PubMed - indexed for MEDLINE]

39: Siegan JB, Hama AT, Sagen J.
Abstract Suppression of neuropathic pain by a naturally-derived peptide with NMDA antagonist activity.
Brain Res. 1997 May 2;755(2):331-4.
PMID: 9175901 [PubMed - indexed for MEDLINE]

40: Bresjanac M, Sagen J, Seigel G, Paino CL, Kordower J, Gash DM.
Abstract Xenogeneic adrenal medulla graft rejection rather than survival leads to increased rat striatal tyrosine hydroxylase immunoreactivity.
J Neuropathol Exp Neurol. 1997 May;56(5):490-8.
PMID: 9143262 [PubMed - indexed for MEDLINE]

41: Siegan JB, Sagen J.
Abstract A natural peptide with NMDA inhibitory activity reduces tonic pain in the formalin model.
Neuroreport. 1997 Apr 14;8(6):1379-81.
PMID: 9172139 [PubMed - indexed for MEDLINE]

42: Siegan JB, Sagen J.
Abstract Attenuation of formalin pain responses in the rat by adrenal medullary transplants in the spinal subarachnoid space.
Pain. 1997 Apr;70(2-3):279-85.
PMID: 9150303 [PubMed - indexed for MEDLINE]

43: Ibuki T, Hama AT, Wang XT, Pappas GD, Sagen J.
Abstract Loss of GABA-immunoreactivity in the spinal dorsal horn of rats with peripheral nerve injury and promotion of recovery by adrenal medullary grafts.
Neuroscience. 1997 Feb;76(3):845-58.
PMID: 9135056 [PubMed - indexed for MEDLINE]

44: Siegan JB, Hama AT, Sagen J.
Abstract Alterations in rat spinal cord cGMP by peripheral nerve injury and adrenal medullary transplantation.
Neurosci Lett. 1996 Aug 30;215(1):49-52.
PMID: 8880751 [PubMed - indexed for MEDLINE]

45: Czech KA, Pollak R, Pappas GD, Sagen J.
Abstract Bovine chromaffin cells for CNS transplantation do not elicit xenogeneic T cell proliferative responses in vitro.
Cell Transplant. 1996 Mar-Apr;5(2):257-67.
PMID: 8689036 [PubMed - indexed for MEDLINE]

46: Wang XT, Pappas GD, Sagen J, Unnerstall JR.
Abstract Cells expressing preproenkephalin mRNA in the rat pineal gland are not serotonin-producing pinealocytes: evidence using in situ hybridization combined with immunocytochemistry for serotonin.
Cell Mol Neurobiol. 1996 Feb;16(1):73-84.
PMID: 8714561 [PubMed - indexed for MEDLINE]

47: Hama AT, Pappas GD, Sagen J.
Abstract Adrenal medullary implants reduce transsynaptic degeneration in the spinal cord of rats following chronic constriction nerve injury.
Exp Neurol. 1996 Jan;137(1):81-93.
PMID: 8566215 [PubMed - indexed for MEDLINE]

48: Wang H, Sagen J.
Abstract Attenuation of pain-related hyperventilation in adjuvant arthritic rats with adrenal medullary transplants in the spinal subarachnoid space.
Pain. 1995 Dec;63(3):313-20.
PMID: 8719531 [PubMed - indexed for MEDLINE]

49: Czech KA, Sagen J.
Abstract Update on cellular transplantation into the CNS as a novel therapy for chronic pain.
Prog Neurobiol. 1995 Aug;46(5):507-29. Review.
PMID: 8532850 [PubMed - indexed for MEDLINE]

50: Hama AT, Unnerstall JR, Siegan JB, Sagen J.
Abstract Modulation of NMDA receptor expression in the rat spinal cord by peripheral nerve injury and adrenal medullary grafting.
Brain Res. 1995 Jul 31;687(1-2):103-13.
PMID: 7583294 [PubMed - indexed for MEDLINE]

51: Sagen J, Wang H.
Abstract Adrenal medullary grafts suppress c-fos induction in spinal neurons of arthritic rats.
Neurosci Lett. 1995 Jun 16;192(3):181-4.
PMID: 7566645 [PubMed - indexed for MEDLINE]

52: Pandey SC, Ren X, Sagen J, Pandey GN.
Abstract Beta-adrenergic receptor subtypes in stress-induced behavioral depression.
Pharmacol Biochem Behav. 1995 Jun-Jul;51(2-3):339-44.
PMID: 7667350 [PubMed - indexed for MEDLINE]

53: Siegan JB, Sagen J.
Abstract Attenuation of NMDA-induced spinal hypersensitivity by adrenal medullary transplants.
Brain Res. 1995 May 22;680(1-2):88-98.
PMID: 7663988 [PubMed - indexed for MEDLINE]

54: Dougherty DD, Sortwell CE, Sagen J.
Abstract Pharmacologic specificity of antidepressive activity by monoaminergic neural transplants.
Psychopharmacology (Berl). 1995 Mar;118(1):10-8.
PMID: 7597115 [PubMed - indexed for MEDLINE]

55: Lazorthes Y, Bes JC, Sagen J, Tafani M, Tkaczuk J, Sallerin B, Nahri I, Verdie JC, Ohayon E, Caratero C, et al.
Abstract Transplantation of human chromaffin cells for control of intractable cancer pain.
Acta Neurochir Suppl. 1995;64:97-100.
PMID: 8748593 [PubMed - indexed for MEDLINE]

56: Schueler SB, Sagen J, Pappas GD, Kordower JH.
Abstract Long-term viability of isolated bovine adrenal medullary chromaffin cells following intrastriatal transplantation.
Cell Transplant. 1995 Jan-Feb;4(1):55-64.
PMID: 7728334 [PubMed - indexed for MEDLINE]

57: Sortwell CE, Pappas GD, Sagen J.
Abstract Chromaffin cell xenografts in the rat neocortex can produce antidepressive activity in the forced swimming test.
Exp Brain Res. 1995;103(1):59-69.
PMID: 7615038 [PubMed - indexed for MEDLINE]

58: Sortwell CE, Petty F, Kramer G, Sagen J.
Abstract In vivo release of catecholamines from xenogeneic chromaffin cell grafts with antidepressive activity.
Exp Neurol. 1994 Nov;130(1):1-8.
PMID: 7821384 [PubMed - indexed for MEDLINE]

59: Sagen J, Ortega JD.
Abstract Influence of the CNS environment on chromaffin cell survival and catecholamine secretion patterns.
J Neurochem. 1994 Sep;63(3):1159-62.
PMID: 8051558 [PubMed - indexed for MEDLINE]

60: Joseph JM, Goddard MB, Mills J, Padrun V, Zurn A, Zielinski B, Favre J, Gardaz JP, Mosimann F, Sagen J, et al.
Abstract Transplantation of encapsulated bovine chromaffin cells in the sheep subarachnoid space: a preclinical study for the treatment of cancer pain.
Cell Transplant. 1994 Sep-Oct;3(5):355-64.
PMID: 7530113 [PubMed - indexed for MEDLINE]

61: Hama AT, Sagen J, Pappas GD.
Abstract Morphological characterization of dorsal horn spinal neurons in rats with unilateral constriction nerve injury: a preliminary study.
Neurol Res. 1994 Aug;16(4):297-304.
PMID: 7984262 [PubMed - indexed for MEDLINE]

62: Hama AT, Sagen J.
Abstract Alleviation of neuropathic pain symptoms by xenogeneic chromaffin cell grafts in the spinal subarachnoid space.
Brain Res. 1994 Jul 18;651(1-2):183-93.
PMID: 7922566 [PubMed - indexed for MEDLINE]

63: Wang H, Sagen J.
Abstract Absence of appreciable tolerance and morphine cross-tolerance in rats with adrenal medullary transplants in the spinal cord.
Neuropharmacology. 1994 May;33(5):681-92.
PMID: 7936104 [PubMed - indexed for MEDLINE]

64: Hama AT, Sagen J.
Abstract Induction of spinal NADPH-diaphorase by nerve injury is attenuated by adrenal medullary transplants.
Brain Res. 1994 Mar 21;640(1-2):345-51.
PMID: 8004464 [PubMed - indexed for MEDLINE]

65: Wang H, Sagen J.
Abstract Optimization of adrenal medullary allograft conditions for pain alleviation.
J Neural Transplant Plast. 1994 Jan-Mar;5(1):49-64.
PMID: 7819372 [PubMed - indexed for MEDLINE]

66: Ortega JD, Sagen J, Pappas GD.
Abstract Origin of afferent projections into bovine chromaffin cell implants in the rat periaqueductal gray determined by retrograde and anterograde tracing.
J Neural Transplant Plast. 1994 Jan-Mar;5(1):31-48.
PMID: 7819371 [PubMed - indexed for MEDLINE]

67: Winnie AP, Pappas GD, Das Gupta TK, Wang H, Ortega JD, Sagen J.
Abstract Subarachnoid adrenal medullary transplants for terminal cancer pain. A report of preliminary studies.
Anesthesiology. 1993 Oct;79(4):644-53.
PMID: 8214743 [PubMed - indexed for MEDLINE]

68: Schueler SB, Ortega JD, Sagen J, Kordower JH.
Abstract Robust survival of isolated bovine adrenal chromaffin cells following intrastriatal transplantation: a novel hypothesis of adrenal graft viability.
J Neurosci. 1993 Oct;13(10):4496-510.
PMID: 8105042 [PubMed - indexed for MEDLINE]

69: Sortwell CE, Sagen J.
Abstract Induction of antidepressive activity by monoaminergic transplants in rat neocortex.
Pharmacol Biochem Behav. 1993 Sep;46(1):225-30.
PMID: 8255915 [PubMed - indexed for MEDLINE]

70: Sagen J, Wang H, Tresco PA, Aebischer P.
Abstract Transplants of immunologically isolated xenogeneic chromaffin cells provide a long-term source of pain-reducing neuroactive substances.
J Neurosci. 1993 Jun;13(6):2415-23.
PMID: 7684773 [PubMed - indexed for MEDLINE]

71: Hama AT, Sagen J.
Abstract Reduced pain-related behavior by adrenal medullary transplants in rats with experimental painful peripheral neuropathy.
Pain. 1993 Feb;52(2):223-31.
PMID: 8384360 [PubMed - indexed for MEDLINE]

72: Ortega JD, Sagen J.
Abstract Pharmacologic characterization of opioid peptide release from chromaffin cell transplants using a brain slice superfusion method.
Exp Brain Res. 1993;95(3):381-7.
PMID: 8224064 [PubMed - indexed for MEDLINE]

73: Garces YI, Rabito SF, Minshall RD, Sagen J.
Abstract Lack of potent antinociceptive activity by substance P antagonist CP-96,345 in the rat spinal cord.
Life Sci. 1993;52(4):353-60.
PMID: 7678436 [PubMed - indexed for MEDLINE]

74: Ortega JD, Sagen J, Pappas GD.
Abstract Survival and integration of bovine chromaffin cells transplanted into rat central nervous system without exogenous trophic factors.
J Comp Neurol. 1992 Sep 1;323(1):13-24.
PMID: 1430313 [PubMed - indexed for MEDLINE]

75: Winn SR, Tresco PA, Zielinski B, Sagen J, Aebischer P.
Abstract Microencapsulated bovine chromaffin cells in vitro: effect of density and coseeding with a NGF-releasing cell line.
J Neural Transplant Plast. 1992 Apr-Sep;3(2-3):115-24.
PMID: 1515479 [PubMed - indexed for MEDLINE]

76: Sagen J.
Abstract Chromaffin cell transplants for alleviation of chronic pain.
ASAIO J. 1992 Jan-Mar;38(1):24-8.
PMID: 1372836 [PubMed - indexed for MEDLINE]

77: Ortega JD, Sagen J, Pappas GD.
Abstract Short-term immunosuppression enhances long-term survival of bovine chromaffin cell xenografts in rat CNS.
Cell Transplant. 1992;1(1):33-41.
PMID: 1364246 [PubMed - indexed for MEDLINE]

78: Aebischer P, Tresco PA, Sagen J, Winn SR.
Abstract Transplantation of microencapsulated bovine chromaffin cells reduces lesion-induced rotational asymmetry in rats.
Brain Res. 1991 Sep 27;560(1-2):43-9.
PMID: 1760745 [PubMed - indexed for MEDLINE]

79: Sagen J, Kemmler JE, Wang H.
Abstract Adrenal medullary transplants increase spinal cord cerebrospinal fluid catecholamine levels and reduce pain sensitivity.
J Neurochem. 1991 Feb;56(2):623-7.
PMID: 1988560 [PubMed - indexed for MEDLINE]

80: Sagen J, Sortwell CE, Pappas GD.
Abstract Monoaminergic neural transplants prevent learned helplessness in a rat depression model.
Biol Psychiatry. 1990 Dec 15;28(12):1037-48.
PMID: 1963093 [PubMed - indexed for MEDLINE]

81: Sagen J, Pappas GD, Ortega JD.
Abstract Host-graft relationships of isolated bovine chromaffin cells in rat periaqueductal grey.
J Neurocytol. 1990 Oct;19(5):697-707.
PMID: 2077111 [PubMed - indexed for MEDLINE]

82: Sagen J, Wang H, Pappas GD.
Abstract Adrenal medullary implants in the rat spinal cord reduce nociception in a chronic pain model.
Pain. 1990 Jul;42(1):69-79.
PMID: 2235000 [PubMed - indexed for MEDLINE]

83: Sagen J, Wang H.
Abstract Prolonged analgesia by enkephalinase inhibition in rats with spinal cord adrenal medullary transplants.
Eur J Pharmacol. 1990 Apr 25;179(3):427-33.
PMID: 2364994 [PubMed - indexed for MEDLINE]

84: Sagen J, Kemmler JE.
Abstract Increased levels of Met-enkephalin-like immunoreactivity in the spinal cord CSF of rats with adrenal medullary transplants.
Brain Res. 1989 Nov 13;502(1):1-10.
PMID: 2819448 [PubMed - indexed for MEDLINE]

85: Pappas GD, Sagen J.
Abstract Fine structural correlates of vascular permeability of chromaffin cell transplants in CNS pain modulatory regions.
Exp Neurol. 1988 Dec;102(3):280-9.
PMID: 3197788 [PubMed - indexed for MEDLINE]

86: Sagen J, Pappas GD.
Abstract Pharmacologic consequences of the vascular permeability of chromaffin cell transplants in CNS pain modulatory regions.
Exp Neurol. 1988 Dec;102(3):290-7.
PMID: 2904375 [PubMed - indexed for MEDLINE]

87: Pappas GD, Sagen J.
No abstract The fine structure of chromaffin cell implants in the pain modulatory regions of the rat periaqueductal gray and spinal cord.
Prog Brain Res. 1988;78:513-20. No abstract available.
PMID: 3247445 [PubMed - indexed for MEDLINE]

88: Sagen J, Proudfit HK.
Abstract Release of endogenous monoamines into spinal cord superfusates following the microinjection of phentolamine into the nucleus raphe magnus.
Brain Res. 1987 Mar 17;406(1-2):246-54.
PMID: 3567625 [PubMed - indexed for MEDLINE]

89: Sagen J, Pappas GD, Perlow MJ.
Abstract Fine structure of adrenal medullary grafts in the pain modulatory regions of the rat periaqueductal gray.
Exp Brain Res. 1987;67(2):380-90.
PMID: 3622696 [PubMed - indexed for MEDLINE]

90: Sagen J, Pappas GD, Perlow MJ.
Abstract Alterations in nociception following adrenal medullary transplants into the rat periaqueductal gray.
Exp Brain Res. 1987;67(2):373-9.
PMID: 3622695 [PubMed - indexed for MEDLINE]

91: Sagen J, Pappas GD.
No abstract Morphological and functional correlates of chromaffin cell transplants in CNS pain modulatory regions.
Ann N Y Acad Sci. 1987;495:306-33. No abstract available.
PMID: 3474947 [PubMed - indexed for MEDLINE]

92: Sagen J, Pappas GD, Perlow MJ.
Abstract Adrenal medullary tissue transplants in the rat spinal cord reduce pain sensitivity.
Brain Res. 1986 Oct 1;384(1):189-94.
PMID: 3790994 [PubMed - indexed for MEDLINE]

93: Sagen J, Pappas GD, Pollard HB.
Free in PMC Analgesia induced by isolated bovine chromaffin cells implanted in rat spinal cord.
Proc Natl Acad Sci U S A. 1986 Oct;83(19):7522-6.
PMID: 3463981 [PubMed - indexed for MEDLINE]

94: Pappas GD, Sagen J.
Abstract Fine structure of PC12 cell implants in the rat spinal cord.
Neurosci Lett. 1986 Sep 25;70(1):59-64.
PMID: 3774220 [PubMed - indexed for MEDLINE]

95: Sagen J, Proudfit HK.
Abstract Alterations in nociception following lesions of the A5 catecholamine nucleus.
Brain Res. 1986 Apr 2;370(1):93-101.
PMID: 3754780 [PubMed - indexed for MEDLINE]

96: Sagen J, Proudfit HK.
Abstract Evidence for pain modulation by pre- and postsynaptic noradrenergic receptors in the medulla oblongata.
Brain Res. 1985 Apr 8;331(2):285-93.
PMID: 2859092 [PubMed - indexed for MEDLINE]

97: Sagen J, Proudfit HK.
Abstract Effect of intrathecally administered noradrenergic antagonists on nociception in the rat.
Brain Res. 1984 Sep 24;310(2):295-301.
PMID: 6548399 [PubMed - indexed for MEDLINE]

98: Sagen J, Winker MA, Proudfit HK.
Abstract Hypoalgesia induced by the local injection of phentolamine in the nucleus raphe magnus: blockade by depletion of spinal cord monoamines.
Pain. 1983 Jul;16(3):253-63.
PMID: 6310470 [PubMed - indexed for MEDLINE]

99: Sagen J, Proudfit HK.
Abstract Hypoalgesia induced by blockade of noradrenergic projections to the raphe magnus: reversal by blockade of noradrenergic projections to the spinal cord.
Brain Res. 1981 Nov 2;223(2):391-6.
PMID: 7284816 [PubMed - indexed for MEDLINE]

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