Jeffrey S Schweitzer1,2, Bin Song3,4, Pierre R Leblanc3,4, Melissa Feitosa3,4, Bob S Carter1,2, Kwang-Soo Kim3,4. 1. Department of Neurosurgery, Massachusetts General Hospital, Boston, Massachusetts. 2. Department of Neurosurgery, Harvard Medical School, Boston, Massachusetts. 3. Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts. 4. Molecular Neurobiology Laboratory, Program in Neuroscience, and Harvard Stem Cell Institute, McLean Hospital, Harvard Medical School, Belmont, Massachusetts.
Abstract
BACKGROUND: Surgical implantation of cellular grafts into the brain is of increasing importance, as stem cell-based therapies for Parkinson and other diseases continue to develop. The effect of grafting technique on development and survival of the graft has received less attention. Rate and method of graft delivery may impact the cell viability and success of these therapies. Understanding the final location of the graft with respect to the intended target location is also critical. OBJECTIVE: To describe a "columnar injection" technique designed to reduce damage to host tissue and result in a column of graft material with greater surface area to volume ratio than traditional injection techniques. METHODS: Using a clinically relevant model system of human embryonic stem cell-derived dopaminergic progenitors injected into athymic rat host brain, we describe a novel device that allows separate control of syringe barrel and plunger, permitting precise deposition of the contents into the cannula tract during withdrawal. Controls consist of contralateral injection using traditional techniques. Graft histology was examined at graft maturity. RESULTS: Bolus grafts were centered on the injection tract but were largely proximal to the "target" location. These grafts displayed a conspicuous peripheral distribution of cells, particularly of mature dopaminergic neurons. In contrast, column injections remained centered at the intended target, contained more evenly distributed cells, and had significantly more mature dopaminergic neurons. CONCLUSION: We suggest that this columnar injection technique may allow better engraftment and development of intracerebral grafts, enhancing outcomes of cell therapy, compared to fixed-point injection techniques.
BACKGROUND: Surgical implantation of cellular grafts into the brain is of increasing importance, as stem cell-based therapies for Parkinson and other diseases continue to develop. The effect of grafting technique on development and survival of the graft has received less attention. Rate and method of graft delivery may impact the cell viability and success of these therapies. Understanding the final location of the graft with respect to the intended target location is also critical. OBJECTIVE: To describe a "columnar injection" technique designed to reduce damage to host tissue and result in a column of graft material with greater surface area to volume ratio than traditional injection techniques. METHODS: Using a clinically relevant model system of human embryonic stem cell-derived dopaminergic progenitors injected into athymic rat host brain, we describe a novel device that allows separate control of syringe barrel and plunger, permitting precise deposition of the contents into the cannula tract during withdrawal. Controls consist of contralateral injection using traditional techniques. Graft histology was examined at graft maturity. RESULTS: Bolus grafts were centered on the injection tract but were largely proximal to the "target" location. These grafts displayed a conspicuous peripheral distribution of cells, particularly of mature dopaminergic neurons. In contrast, column injections remained centered at the intended target, contained more evenly distributed cells, and had significantly more mature dopaminergic neurons. CONCLUSION: We suggest that this columnar injection technique may allow better engraftment and development of intracerebral grafts, enhancing outcomes of cell therapy, compared to fixed-point injection techniques.
Authors: Kai-C Sonntag; Bin Song; Nayeon Lee; Jin Hyuk Jung; Young Cha; Pierre Leblanc; Carolyn Neff; Sek Won Kong; Bob S Carter; Jeffrey Schweitzer; Kwang-Soo Kim Journal: Prog Neurobiol Date: 2018-04-11 Impact factor: 11.685
Authors: Wen Li; Elisabet Englund; Håkan Widner; Bengt Mattsson; Danielle van Westen; Jimmy Lätt; Stig Rehncrona; Patrik Brundin; Anders Björklund; Olle Lindvall; Jia-Yi Li Journal: Proc Natl Acad Sci U S A Date: 2016-05-02 Impact factor: 11.205
Authors: T B Freeman; C W Olanow; R A Hauser; G M Nauert; D A Smith; C V Borlongan; P R Sanberg; D A Holt; J H Kordower; F J Vingerhoets Journal: Ann Neurol Date: 1995-09 Impact factor: 10.422
Authors: C Warren Olanow; Christopher G Goetz; Jeffrey H Kordower; A Jon Stoessl; Vesna Sossi; Mitchell F Brin; Kathleen M Shannon; G Michael Nauert; Daniel P Perl; James Godbold; Thomas B Freeman Journal: Ann Neurol Date: 2003-09 Impact factor: 10.422
Authors: Jeffrey S Schweitzer; Bin Song; Todd M Herrington; Tae-Yoon Park; Nayeon Lee; Sanghyeok Ko; Jeha Jeon; Young Cha; Kyungsang Kim; Quanzheng Li; Claire Henchcliffe; Michael Kaplitt; Carolyn Neff; Otto Rapalino; Hyemyung Seo; In-Hee Lee; Jisun Kim; Taewoo Kim; Gregory A Petsko; Jerome Ritz; Bruce M Cohen; Sek-Won Kong; Pierre Leblanc; Bob S Carter; Kwang-Soo Kim Journal: N Engl J Med Date: 2020-05-14 Impact factor: 91.245