Pozzi Sara, Lisini Daniela, Podestà Marina, Bernardo Maria Ester, Sessarego Nadia, Piaggio Giovanna, Cometa Angela, Giorgiani Giovanna, Mina Tommaso, Buldini Barbara, Maccario Rita, Frassoni Francesco, Locatelli Franco
Centro Cellule Staminali e Terapia Cellulare, Ospedale San Martino, Genova, Italy.
Exp Hematol. 2006 Jul;34(7):934-42. doi: 10.1016/j.exphem.2006.03.007.
Multipotent mesenchymal stromal cells (MSCs) are endowed with multilineage differentiative potential and immunomodulatory properties. It is still a matter of debate whether donor MSCs have sustained engraftment potential in host bone marrow (BM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of this study was to analyze the donor/recipient origin of MSCs in children receiving allogeneic either BM or cord blood (CB) transplantation.
Thirty-seven pediatric patients undergoing allo-HSCT for either a malignant or a nonmalignant disorder were enrolled in the study; 19 received CB and 18 BM transplantation. Results were compared with those obtained in 14 adults given BM transplantation for either malignant or nonmalignant disorders. MSCs were grown from BM aspirates obtained 1-17 and 2-192 months after allo-HSCT in pediatric and adult patients, respectively. MSC samples at the third-fourth passage were phenotypically characterized. Donor/recipient origin of MSCs was assessed by amelogenin assay and microsatellite analysis.
MSCs could be grown from 30 of 37 children; at the third-fourth passage MSCs resulted positive (> or = 98%) for CD73, CD105, CD106, CD29, CD13, CD44 and negative (< or = 1%) for CD34, CD45, CD14. Mixed chimerism with donor cells was observed in 4 BM and 5 CB transplantation recipients, respectively; full recipient chimerism was detected in the remaining children. Full recipient MSC chimerism was observed also in all assessable (12/14) adult patients.
BM of pediatric patients might be a more favorable milieu than that of adults for sustained engraftment of transplanted MSCs. MSCs able to engraft in the host can be transferred with cryopreserved CB units.
多能间充质基质细胞(MSCs)具有多向分化潜能和免疫调节特性。同种异体造血干细胞移植(allo-HSCT)后供体MSCs在宿主骨髓(BM)中是否具有持续植入潜能仍存在争议。本研究旨在分析接受同种异体骨髓或脐血(CB)移植的儿童中MSCs的供体/受体来源。
37例因恶性或非恶性疾病接受allo-HSCT的儿科患者纳入研究;19例接受CB移植,18例接受BM移植。将结果与14例因恶性或非恶性疾病接受BM移植的成人患者的结果进行比较。分别从allo-HSCT后1 - 17个月和2 - 192个月获得的儿科和成人患者的骨髓抽吸物中培养MSCs。对传代三至四代的MSC样本进行表型特征分析。通过牙釉蛋白检测和微卫星分析评估MSCs的供体/受体来源。
37名儿童中有30名能够培养出MSCs;传代三至四代时,MSCs的CD73、CD105、CD106、CD29、CD13、CD44呈阳性(≥98%),CD34、CD45、CD14呈阴性(≤1%)。分别在4例BM移植受者和5例CB移植受者中观察到与供体细胞的混合嵌合现象;其余儿童检测到完全受体嵌合。在所有可评估的(12/14)成人患者中也观察到完全受体MSC嵌合现象。
与成人相比,儿科患者的骨髓可能是移植MSCs持续植入更有利的环境。能够植入宿主的MSCs可以通过冷冻保存的CB单位进行转移。