title: The therapeutic potential of ex vivo expanded CD133+ cells derived from human peripheral blood for peripheral nerve injuries.
abstract: OBJECTIVE
  CD133(+) cells have the potential to enhance histological and functional recovery from peripheral nerve injury. However, the number of CD133(+) cells safely obtained from human peripheral blood is extremely limited. To address this issue, the authors expanded CD133(+) cells derived from human peripheral blood using the serum-free expansion culture method and transplanted these ex vivo expanded cells into a model of sciatic nerve defect in rats. The purpose of this study was to determine the potential of ex vivo expanded CD133(+) cells to induce or enhance the repair of injured peripheral nerves.
  
  
  METHODS
  Phosphate-buffered saline (PBS group [Group 1]), 10(5) fresh CD133(+) cells (fresh group [Group 2]), 10(5) ex vivo expanded CD133(+) cells (expansion group [Group 3]), or 10(4) fresh CD133(+) cells (low-dose group [Group 4]) embedded in atelocollagen gel were transplanted into a silicone tube that was then used to bridge a 15-mm defect in the sciatic nerve of athymic rats (10 animals per group). At 8 weeks postsurgery, histological and functional evaluations of the regenerated tissues were performed.
  
  
  RESULTS
  After 1 week of expansion culture, the number of cells increased 9.6 ± 3.3-fold. Based on the fluorescence-activated cell sorting analysis, it was demonstrated that the initial freshly isolated CD133(+) cell population contained 93.22% ± 0.30% CD133(+) cells and further confirmed that the expanded cells had a purity of 59.02% ± 1.58% CD133(+) cells. However, the histologically and functionally regenerated nerves bridging the defects were recognized in all rats in Groups 2 and 3 and in 6 of 10 rats in Group 4. The nerves did not regenerate to bridge the defect in any of the rats in Group 1.
  
  
  CONCLUSIONS
  The authors' results show that ex vivo expanded CD133(+) cells derived from human peripheral blood have a therapeutic potential similar to fresh CD133(+) cells for peripheral nerve injuries. The ex vivo procedure that can be used to expand CD133(+) cells without reducing their function represents a novel method for developing cell therapy for nerve defects in a clinical setting.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. ohtsubo0529@yahoo.co.jp
authors.forename: Shin
authors.initials: S
authors.lastname: Ohtsubo
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Naosuke
authors.initials: N
authors.lastname: Kamei
authors.forename: Yasumu
authors.initials: Y
authors.lastname: Kijima
authors.forename: Osami
authors.initials: O
authors.lastname: Suzuki
authors.forename: Toru
authors.initials: T
authors.lastname: Sunagawa
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Higashi
authors.forename: Haruchika
authors.initials: H
authors.lastname: Masuda
authors.forename: Takayuki
authors.initials: T
authors.lastname: Asahara
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Ochi
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D023421:Models, Animal; D009416:Nerve Regeneration; D010455:Peptides / Q000378:metabolism*; D059348:Peripheral Nerve Injuries / Q000628:therapy*; D051381:Rats; D011916:Rats, Inbred F344; D011923:Rats, Nude; D020127:Recovery of Function; D012584:Sciatic Nerve / Q000293:injuries*; D016896:Treatment Outcome
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606025:Prom1 protein, rat