Microencapsulated Bovine Chromaffin Cell Xenografts into Hemiparkinsonian Rats: A Drug‐Induced Rotational Behavior and Histological Changes Analysis

Xue, Yuan; Gao, Jian; Xi, Zengfei; Wang, Zhenfu; Li, Xinjian; Cui, Xin; Luo, Yun; Li, Chonghui; Wang, Luning; Zhou, Daojin; Sun, Richard; Sun, Anthony M.

doi:10.1046/j.1525-1594.2001.025002131.x

Cited by 26 publications

(9 citation statements)

References 33 publications

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“…Alginate encapsulation of other cell types has been shown to provide therapeutic physiological benefits after grafting experiments in animal models of malignant glioma (Joki et al, 2001), liver failure (Hirai et al, 1993), hemophilia (Hortelano et al, 1996), diabetes (Sun et al, 1996), Parkinson's disease (Xue et al, 2001), and growth hormone deficiency (Cheng et al, 1998). To our knowledge, these are the first results documenting behavioral recovery due to alginate encapsulated genetically engineered cells after spinal cord injury.…”

Section: Figmentioning

confidence: 89%

Alginate Encapsulated BDNF-Producing Fibroblast Grafts Permit Recovery of Function after Spinal Cord Injury in the Absence of Immune Suppression

Tobias

Han²,

Shumsky³

et al. 2005

Journal of Neurotrauma

118

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Encapsulation of cells has the potential to provide a protective barrier against host immune cell interactions after grafting. Previously we have shown that alginate encapsulated BDNF-producing fibroblasts (Fb/BDNF) survived for one month in culture, made bioactive neurotrophins, survived transplantation into the injured spinal cord in the absence of immune suppression, and provided a permissive environment for host axon growth. We extend these studies by examining the effects of grafting encapsulated Fb/BDNF into a subtotal cervical hemisection on recovery of forelimb and hindlimb function and axonal growth in the absence of immune suppression. Grafting of encapsulated Fb/BDNF resulted in partial recovery of forelimb usage in a test of vertical exploration and of hindlimb function while crossing a horizontal rope. Recovery was significantly greater compared to animals that received unencapsulated Fb/BDNF without immune suppression, but similar to that of immune suppressed animals receiving unencapsulated Fb/BDNF. Immunocytochemical examination revealed neurofilament (RT-97), 5-HT, CGRP and GAP-43 containing axons surrounding encapsulated Fb/BDNF within the injury site, indicating axonal growth. BDA labeling however showed no evidence of regeneration of rubrospinal axons in recipients of encapsulated Fb/BDNF, presumably because the amounts of BDNF available from the encapsulated grafts are substantially less than those provided by the much larger numbers of Fb/BDNF grafted in a gelfoam matrix in the presence of immune suppression. These results suggest that plasticity elicited by the BDNF released from the encapsulated cells contributed to reorganization that led to behavioral recovery in these animals and that the behavioral recovery could proceed in the absence of rubrospinal tract regeneration. Alginate encapsulation is therefore a feasible strategy for delivery of therapeutic products produced by non-autologous engineered fibroblasts and provides an environment suitable for recovery of lost function in the injured spinal cord.

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Section: Figmentioning

confidence: 89%

Alginate Encapsulated BDNF-Producing Fibroblast Grafts Permit Recovery of Function after Spinal Cord Injury in the Absence of Immune Suppression

Tobias

Han²,

Shumsky³

et al. 2005

Journal of Neurotrauma

118

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“…Alginate membranes, either alone or in conjunction with a supporting polycationic component, have been used to deliver cell therapy products for the treatment of diabetes, [1][2][3][4][5][6][7][8] chronic pain, 9 hemophilia, 10,11 central nervous system (CNS) disorders, [12][13][14][15][16][17][18][19][20][21][22] and others. Because of the diversity of clinical indications that alginate cell containing capsules can potentially be used for, alginate beads have been implanted into the peritoneum, 23 the subcutaneous space, 24,25 the kidney capsule, 26 the portal circulation, 27,28 the brain parenchyma, 13,22 the spinal cord, 29 the cochlea, 30 and have been used for oral delivery. 31 Encouraging results have been reported using each of these transplant sites but the majority of studies are short term, graft survival is typically variable, and clear cut, reproducible clinical success has not been achieved.…”

Section: Introductionmentioning

confidence: 99%

“…While its use is inherently appealing, its success has been precluded by inconsistent performance. Alginate membranes, either alone or in conjunction with a supporting polycationic component, have been used to deliver cell therapy products for the treatment of diabetes, 1-8 chronic pain, 9 hemophilia, 10,11 central nervous system (CNS) disorders, [12][13][14][15][16][17][18][19][20][21][22] and others.…”

Section: Introductionmentioning

confidence: 99%

Stability of alginate‐polyornithine microcapsules is profoundly dependent on the site of transplantation

Thanos

Bintz

Emerich

2006

J Biomedical Materials Res

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Alginate encapsulation is a form of cell-based therapy with numerous preclinical successes but recalcitrant complications related to stability and reproducibility. Understanding how alginate stability varies across different transplant sites will help identify indications that might benefit most from this approach. Alginate stability has been quantified in the peritoneum, but there are no systematic studies comparing its relative stability across transplant sites. This study compares the stability of alginate-polycation microcapsules implanted in the peritoneum to those implanted in the brain and subcutaneous space at 14, 28, 60, 90, 120, and 180 days in-life. Using Fourier-Transform Infrared Spectroscopy (FTIR), the surface of explanted capsules was analyzed for the relative proportion of alginate (outer coat) and the polycationic polyornithine (middle coat). Using a mathematic relationship between FTIR peaks related to these two material components, an index was generated to compare the stability of four different alginates. A notable difference was observed with rapid breakdown in the peritoneum. Conversely, identical alginate capsules transplanted into the brain or subcutaneous space were stable for the 6 month study. These data suggest that (1) successful intraperitoneal transplantation requires modifications of the capsule configuration, the host environment, or both and (2) that sites such as the brain and subcutaneous space are inherently less hostile to conventional alginate capsule configurations.

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“…Microencapsulation is used to contain and immuno‐protect cells used in cell‐based drug therapy. Cell‐based drug therapy enables direct, continuous supply of drugs in difficult to access sites and has been studied in transplantation models of Parkinson's disease,1, 2 Alzheimer's disease,3 chronic pain syndrome4, 5 as well as for localized predrug activation in pancreatic cancer treatment 6. Cell‐based drug therapy also enables physiologically responsive drug delivery, and the treatment of type I diabetes by transplantation of insulin‐producing cells has been the major focal interest of this approach and was shown to be successful in reversing diabetes in an animal model 7.…”

Section: Introductionmentioning

confidence: 99%

Assembly of multilayer PSS/PAH membrane on coherent alginate/PLO microcapsule for long‐term graft transplantation

Leung

Trau

Nielsen

2008

J Biomedical Materials Res

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Conventional alginate/poly-L-ornithine (AP) membranes used to immunoisolate foreign tissue transplants fail in long-term transplantations of immortal cell lines. We have developed a novel layer-by-layer (LbL) membrane using polystyrene sulfonate and polyallylamine hydrochloride (PSS/PAH) on top of the coherent AP membrane. Assembly of the LbL membrane was followed by electrophoresis, and the surface morphologies and structure were characterized and examined by cryo-scanning electron microscope and transmission electron microscopy. Unlike the standard AP membrane, the LbL membrane withstood the internal pressure generated by continuous cell proliferation of microencapsulated HEK-293 and Min-6 cells. The new membrane did not affect insulin secretion or diffusion by Min-6 cells.

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Microencapsulated Bovine Chromaffin Cell Xenografts into Hemiparkinsonian Rats: A Drug‐Induced Rotational Behavior and Histological Changes Analysis

Cited by 26 publications

References 33 publications

Alginate Encapsulated BDNF-Producing Fibroblast Grafts Permit Recovery of Function after Spinal Cord Injury in the Absence of Immune Suppression

Alginate Encapsulated BDNF-Producing Fibroblast Grafts Permit Recovery of Function after Spinal Cord Injury in the Absence of Immune Suppression

Stability of alginate‐polyornithine microcapsules is profoundly dependent on the site of transplantation

Assembly of multilayer PSS/PAH membrane on coherent alginate/PLO microcapsule for long‐term graft transplantation

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