Castello Sandra, Podestà Marina, Menditto Vincenzo G, Ibatici Adalberto, Pitto Anna, Figari Osvaldo, Scarpati Daniele, Magrassi Lorenzo, Bacigalupo Andrea, Piaggio Giovanna, Frassoni Francesco
Centro Cellule Staminali e Terapia Cellularee, Università di Pavia, Italy.
Exp Hematol. 2004 Aug;32(8):782-7. doi: 10.1016/j.exphem.2004.05.026.
Intravenous (IV) injection is currently the normal method for transplanting hematopoietic cells. However, the problem of seeding efficiency and homing is relevant especially when a limited number of stem cells is available. Intra-bone marrow (IBM) injection of bone marrow cells (BMCs) may overcome this problem.
Irradiated (750 cGy) C57BL/6J mice were transplanted with 1 x 10(5) BMCs harvested from transgenic mice expressing an enhanced version of the green fluorescent protein (EGFP+) via IBM or with 1 x 10(6) EGFP+ BMCs via IV. Irradiated (320 cGy) NOD/SCID mice were transplanted with 1 x 10(6) human cord blood (CB) cells via IBM or with 1 x 10(7) human CB cells via IV.
In C57BL/6J mice after 90 days, the fraction of EGFP+ cells harvested was 37% and 53% in IV-treated and IBM-treated (contralateral tibia and femur in the IBM) mice, respectively: the expansion folds were 114 and 1760, respectively. In NOD/SCID mice, the percentages of CD45+ cells and CD45+/CD34+ cells were, at 30 days, 3.3% and 0.3% in IV-treated mice, and 4.4% and 1.1% in IBM-treated mice. At 60 days, the percentages of CD45+ cells and CD45+/CD34+ cells were 2.1% and 0.3% in IV-treated mice and 1.4% and 0.4% in IBM-treated mice. At day 90 the percentages of CD45+ cells and CD45+/CD34+ cells were 3% and 0.3% in IV-treated mice and 2.3% and 0.4% in IBM-treated mice.
Our data demonstrate that IBM transplantation is associated with a seeding efficiency 15 times greater than IV transplantation. IBM transplantation may improve the results of transplant and may be useful in several settings: 1) when a limited number of hematopoietic progenitors are available; and 2) in experiments aiming to place in the bone marrow stem cells of other lineages (CNS, muscle, etc.).
静脉注射目前是移植造血细胞的常规方法。然而,尤其是当可用的干细胞数量有限时,植入效率和归巢问题就显得很重要。骨髓内(IBM)注射骨髓细胞(BMC)可能会克服这个问题。
将经辐照(750 cGy)的C57BL/6J小鼠通过IBM移植1×10⁵个从表达增强型绿色荧光蛋白(EGFP⁺)的转基因小鼠收获的BMC,或通过静脉注射移植1×10⁶个EGFP⁺ BMC。将经辐照(320 cGy)的NOD/SCID小鼠通过IBM移植1×10⁶个人类脐带血(CB)细胞,或通过静脉注射移植1×10⁷个人类CB细胞。
在C57BL/6J小鼠中,90天后,静脉注射处理组和IBM处理组(IBM处理组为对侧胫骨和股骨)收获的EGFP⁺细胞比例分别为37%和53%;扩增倍数分别为114和1760。在NOD/SCID小鼠中,静脉注射处理组在30天时CD45⁺细胞和CD45⁺/CD34⁺细胞的百分比分别为3.3%和0.3%,IBM处理组为4.4%和1.1%。在60天时,静脉注射处理组CD45⁺细胞和CD45⁺/CD34⁺细胞的百分比分别为2.1%和0.3%,IBM处理组为1.4%和0.4%。在90天时,静脉注射处理组CD45⁺细胞和CD45⁺/CD34⁺细胞的百分比分别为3%和0.3%,IBM处理组为2.3%和0.4%。
我们的数据表明,IBM移植的植入效率比静脉注射移植高15倍。IBM移植可能会改善移植结果,并且在以下几种情况下可能有用:1)当可用的造血祖细胞数量有限时;2)在旨在将其他谱系(中枢神经系统、肌肉等)的干细胞植入骨髓的实验中。