Cell transplantation as a treatment for spinal cord injury is a promising therapeutic strategy whose effective clinical application would be facilitated by non-invasive delivery protocols. Cells derived from the bone marrow are particularly attractive because they can be obtained easily, expanded to large numbers and potentially used for autologous as well as allogeneic transplantation. In this study we tested the feasibility of a novel minimally invasive method-lumbar puncture (LP)-for transplanting bone marrow stromal stem cells (MSC) into a clinically relevant spinal cord contusion model. We further sought to determine optimal protocols for performing such minimally invasive cell transplantation. Sprague-Dawley rats received a moderate contusion injury at the midthoracic level followed by LP transplantation of MSC derived from transgenic rats that express the human placental alkaline phosphatase (AP) reporter gene. The recipients were analyzed histologically to evaluate the extent of cell delivery and survival at the injury site. We found that MSC delivered by LP reached the contused spinal cord tissues and exerted a significant beneficial effect by reducing cyst and injury size. Transplantation within 14 days of injury provided significantly greater grafting efficiency than more delayed delivery, and increasing MSC dosage improved cell engraftment. The techniques described here can easily be translated to patients, thus accelerating clinical application of stem cell therapies.
机构:
Kitano Hosp, Tazuke Kofukai Med Res Inst, Dept Plast & Reconstruct Surg, Kita Ku, Osaka 5308507, JapanKitano Hosp, Tazuke Kofukai Med Res Inst, Dept Plast & Reconstruct Surg, Kita Ku, Osaka 5308507, Japan
Suzuki, Yoshihisa
Ishikawa, Namiko
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Kitano Hosp, Tazuke Kofukai Med Res Inst, Dept Plast & Reconstruct Surg, Kita Ku, Osaka 5308507, JapanKitano Hosp, Tazuke Kofukai Med Res Inst, Dept Plast & Reconstruct Surg, Kita Ku, Osaka 5308507, Japan
Ishikawa, Namiko
Omae, Kaoru
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Translat Res Informat Ctr, Kobe, Hyogo, JapanKitano Hosp, Tazuke Kofukai Med Res Inst, Dept Plast & Reconstruct Surg, Kita Ku, Osaka 5308507, Japan
Omae, Kaoru
Hirai, Tatsuya
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Kitano Hosp, Tazuke Kofukai Med Res Inst, Dept Plast & Reconstruct Surg, Kita Ku, Osaka 5308507, JapanKitano Hosp, Tazuke Kofukai Med Res Inst, Dept Plast & Reconstruct Surg, Kita Ku, Osaka 5308507, Japan
Hirai, Tatsuya
Ohnishi, Katsunori
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Ikesucho Clin, Kyoto, JapanKitano Hosp, Tazuke Kofukai Med Res Inst, Dept Plast & Reconstruct Surg, Kita Ku, Osaka 5308507, Japan
Ohnishi, Katsunori
Nakano, Norihiko
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Aino Univ, Fac Nursing & Rehabil, Inst Regenerat & Rehabil, Osaka, JapanKitano Hosp, Tazuke Kofukai Med Res Inst, Dept Plast & Reconstruct Surg, Kita Ku, Osaka 5308507, Japan
Nakano, Norihiko
Nishida, Hidetaka
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Nakayama Vet Hosp, Nara, JapanKitano Hosp, Tazuke Kofukai Med Res Inst, Dept Plast & Reconstruct Surg, Kita Ku, Osaka 5308507, Japan
Nishida, Hidetaka
Nakatani, Toshio
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Kansai Med Univ, Emergency & Crit Care Ctr, Moriguchi, Osaka 570, JapanKitano Hosp, Tazuke Kofukai Med Res Inst, Dept Plast & Reconstruct Surg, Kita Ku, Osaka 5308507, Japan
Nakatani, Toshio
Fukushima, Masanori
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Translat Res Informat Ctr, Kobe, Hyogo, JapanKitano Hosp, Tazuke Kofukai Med Res Inst, Dept Plast & Reconstruct Surg, Kita Ku, Osaka 5308507, Japan
机构:Yale Univ, Sch Med, Neurosci Res Ctr 127A, Vet Affairs Med Ctr,Dept Neurol, West Haven, CT 06516 USA
Akiyama, Y
Radtke, C
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机构:Yale Univ, Sch Med, Neurosci Res Ctr 127A, Vet Affairs Med Ctr,Dept Neurol, West Haven, CT 06516 USA
Radtke, C
Kocsis, JD
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Yale Univ, Sch Med, Neurosci Res Ctr 127A, Vet Affairs Med Ctr,Dept Neurol, West Haven, CT 06516 USAYale Univ, Sch Med, Neurosci Res Ctr 127A, Vet Affairs Med Ctr,Dept Neurol, West Haven, CT 06516 USA
Kocsis, JD
JOURNAL OF NEUROSCIENCE,
2002,
22
(15):
: 6623
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6630