Niemeyer P, Vohrer J, Schmal H, Kasten P, Fellenberg J, Suedkamp N P, Mehlhorn A T
Department of Orthopedic Surgery and Traumatology, Freiburg University Hospital, Freiburg, Germany.
Cytotherapy. 2008;10(8):784-95. doi: 10.1080/14653240802419302.
Mesenchymal stromal cells (MSC) represent an attractive cell population for tissue engineering purposes. As MSC are described as immunoprivileged, non-autologous applications seem possible. A basic requirement is the survival of MSC after transplantation in the host. The purpose of the current paper was to evaluate the survival of undifferentiated and osteogenically induced human MSC from different origins after transplantation in immunocompetent mice.
Human MSC were isolated from bone marrow (BMSC) and adipose tissue (ASC). After cultivation on mineralized collagen, MSC were transplanted subcutaneously into immunocompetent mice (n=12). Undifferentiated MSC (group A) were compared with osteogenic-induced MSC (group B). Human-specific in situ hybridization and anti-vimentin staining was used to follow MSC after transplantation. Quantitative evaluation of lymphocytes and macrophages was performed as a measure of immunologic rejection. Unloaded scaffolds served as controls (group C). Specimens were harvested at 4 and 8 weeks.
Undifferentiated BMSC and ASC were detected in the majority of cases after xenogenic transplantation (group A, a total of 22 out of 24 cases), while osteogenic-induced MSC (group B) could be detected in only three of 24 cases. Quantification of lymphocytes and macrophages revealed significantly higher cell numbers in group B compared with group A (P<0.05).
Our results suggest that undifferentiated MSC are candidates for non-autologous cell transplantation, while osteogenic-induced MSC seem to be eliminated by the host's immune system. This observation seems independent of the origin of MSC and applies to BMSC and ASC.
间充质基质细胞(MSC)是组织工程领域颇具吸引力的细胞群体。由于MSC被认为具有免疫特权,非自体应用似乎是可行的。一个基本要求是MSC在移植到宿主体内后能够存活。本文的目的是评估不同来源的未分化和经成骨诱导的人MSC在免疫活性小鼠体内移植后的存活情况。
从骨髓(BMSC)和脂肪组织(ASC)中分离出人MSC。在矿化胶原上培养后,将MSC皮下移植到免疫活性小鼠体内(n = 12)。将未分化的MSC(A组)与经成骨诱导的MSC(B组)进行比较。移植后使用人特异性原位杂交和抗波形蛋白染色来追踪MSC。对淋巴细胞和巨噬细胞进行定量评估,作为免疫排斥的指标。未负载细胞的支架用作对照(C组)。在4周和8周时采集样本。
异种移植后,大多数情况下能检测到未分化的BMSC和ASC(A组,24例中有22例),而经成骨诱导的MSC(B组)在24例中仅3例可检测到。淋巴细胞和巨噬细胞的定量分析显示,B组的细胞数量明显高于A组(P<0.05)。
我们的结果表明,未分化的MSC是非自体细胞移植的候选者,而经成骨诱导的MSC似乎会被宿主的免疫系统清除。这一观察结果似乎与MSC的来源无关,适用于BMSC和ASC。