Transplantation, of neurons

Ideally biomarkers of activity should be identified at various times over the course of the study to support the pharmacodynamic activity (e.g., normalization of insulin, improvement in beta cell function as measured by C-peptide level, or control of glucose following transplantation of P pancreatic islet cells) improvement of motor coordination in mice with spinal cord damage following transplant of neurons or repair of heart function (e.g., functional measures such as LV ejection fraction, pressure volume loops, ventricular pressure and heart wall thickness). Such markers may also be useful in subsequent clinical... 

Cejas PJ, Martinez M, Karmally S, McKiUop M, McKillop JP, Lunkett JA, Oudega M, Eaton MJ (2000) Lumbar transplant of neurons genetically modified to secrete brain-derived neurotrophic factor attenuates allodynia and hyperalgesia after sciatic nerve constriction. Pain 86 ... 

A variety of observations of axon growth both during normal development and in response to surgical transplantation of neuronal targets (reviewed in Goodman and Shatz, 1993) also provide indirect support for chemotropic guidance cues in vertebrates. 

Freed,C.R.,Greene,P.E.,Breeze,R. E.etal.Transplantation of embryonic dopamine neurons for severe Parkinson s disease [Comment]. N. Engl. J. Med. 344 710-719, 2001. 

NGF chemically conjugated to 0X26 6.2 pg/ injection i.v. injection 4x every 2 weeks Rat intraocular forebrain Survival of cholin-transplant ergic neurons ... 

Macklis, J.D. (1993). Transplanted neocortical neurons migrate selectively into regions of neuronal degeneration produced by chromophore-targeted laser photolysis. J Neurosci, 13,3848-63. 

A population of desired cell types that have the potential to produce new tissues should be generated. The potential of embryonic totipotent stem cells could be exploited in the transplantation of retinal pigment epithelium, myocardial progenitor cells capable of restoring cardiac function and contractility, dopaminergic neurons for the treatment of Parkinson s disease, pancreatic cells for the treatment of diabetes, and others.55... 

Foetal mesencephalic tissue has been implanted in the striatum of patients with the juvenile form of Parkinson s disease and has been shown to develop functional axons this has enabled the dose of L-dopa to be reduced. Both imaging and pharmacological studies have now shown that functional dopaminergic neurons can develop in the brain of the patient following tissue transplantation. However, a major ethical objection has been raised to such transplants as six to seven foetal brains are required to obtain sufficient tissue. In addition, only about 20% of neurons survive transplantation. The ethical problem may be overcome by using brain transplants from domestic animals such as pigs. Such xenotransplants have been shown to survive in the human brain but the main problem with the extensive use of such transplants is the possible spread of viruses and prion infections. 

Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ, Eidelberg D, Fahn S (2001) Transplantation of embryonic dopamine neurons for severe... 

Embryonic stem cells can proliferate indefinitely and under certain condition they can differentiate to neurons and gha in the laboratory. Even though they hold the promise of being able to repair or replace cells or tissues that are damaged or destroyed in neurodegenerative disorders, transplantation of embryonic stem cells is not feasible with current techniques. The lines of... 

In animal models of HD, transplanted striatal cells have survived, grow n and established afferent and efferent connections (Freeman et al., 2000). One open label human trial indicated that grafts may have restored function (Hauser et al., 2002). Recipients show ed cognitive and motor improvements thatw ere associated wdth reductions in striatal and cortical hypometaboiism. The success of grafting may be sensitive to the age of the donor and to the degree of neuronal loss in the patient. Clinical trials are in early phases and there still needs to be resolution of a number of technical issues (Gardian and Vecsei, 2004). 

---