Fetal-Tissue Transplantation for Huntington's Disease: Preclinical Studies

Author(s):  
Paul R. Sanberg ◽  
Cesario V. Borlongan ◽  
Klas Wictorin ◽  
Ole Isacson
1995 ◽  
Vol 4 (6) ◽  
pp. 539-545
Author(s):  
Thomas B. Freeman ◽  
Paul R. Sanberg ◽  
Ole Isacson

Fetal neural transplantation has recently been demonstrated to ameliorate motor and other behavioral deficits in animal models of Huntington's disease, and reconstruct many of the damaged striatal circuits. However, there has been significant variability in the histological appearance of these grafts, most likely related to differences of the regions of dissection of the donor tissue. Selective dissection and transplantation of the lateral ventricular eminence in rodents has resulted in grafts consisting of primarily striatal-like tissue. This data, combined with data from our own and other laboratories has led to a description of the development of the human striatum, with a particular emphasis on the relevance of human striatal development to the field of fetal tissue transplantation for the treatment of Huntington's disease. If the goal of transplantation is to graft GABAergic striatal projection neurons, it is our impression that optimal grafting results will occur when transplants are derived from the lateral ventricular eminence and the lateral aspect of the body of the ventricular eminence anterior to the foramen of Monro. Optimal results are likely to occur when donor ages range from Stage 19 to 23, with possible graft success when donor age extends to as late as postovulatory week 22.


1998 ◽  
Vol 7 (2) ◽  
pp. 131-135 ◽  
Author(s):  
Cesario V. Borlongan ◽  
Theodore K. Koutouzis ◽  
Stephen G. Poulos ◽  
Samuel Saporta ◽  
Paul R. Sanberg

We investigated the 3-nitropropionic acid (3-NP)–induced hypoactive model of Huntington's disease (HD) to demonstrate whether fetal tissue transplantation can ameliorate behavioral deficits associated with a more advanced stage of HD. Twelve-week-old Sprague–Dawley rats were introduced to the 3-NP dosing regimen (10 mg/kg, i.p., once every 4 days for 28 consecutive days), and were then tested for general spontaneous locomotor activity in the Digiscan locomotor apparatus. All rats displayed significant hypoactivity compared to their pre-3-NP injection locomotor activity. Randomly selected rats then received bilateral intrastriatal solid grafts of fetal striatal (lateral ganglionic eminence, LGE) tissues from embryonic day 14 rat fetuses. Approximately 1/3 of each LGE in hibernation medium was infused into each lesioned host striatum. In control rats, medium alone was infused intrastriatally. A 3-mo posttransplant maturation period was allowed prior to locomotor activity testing. Animals receiving fetal LGE grafts exhibited a significant increase in locomotor activity compared to their post-3-NP injection activity or to the controls’ posttransplant activity. Surviving striatal grafts were noted in functionally recovered animals. This observation supports the use of fetal striatal transplants to correct the akinetic stage of HD. To the best of our knowledge, this is the first study that has investigated the effects of fetal striatal transplantation in a hypoactive model of HD.


1993 ◽  
Vol 12 (9) ◽  
pp. 65-67
Author(s):  
Margarita Cancio ◽  
Thomas Rushton ◽  
Thomas B. Freeman ◽  
C.W. Olanow ◽  
John S. Sarzier ◽  
...  

2002 ◽  
Vol 10 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Fu-In Tang ◽  
Shuh-Jen Sheu ◽  
Ching-Huey Chen ◽  
Yun Wang ◽  
Shinn-Zong Lin

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