Attempt to treat congenital pseudarthrosis of the tibia with mesenchymal stromal cell transplantation.
OBJECTIVE
Congenital pseudarthrosis of the tibia (CPT) caused by neurofibromatosis type 1 (NF1) is a refractory disease occurring in childhood. We present two cases that had failed all earlier treatment attempts and, as a last treatment attempt, the patients were chosen to receive mesenchymal stromal cell (MSC) transplantation prior to amputation.


METHODS
The MSC from bone marrow (BM) were harvested from the iliac crest and cultured in osteoinductive medium for 3 weeks. The cultured MSC were injected in solution into BM canals of the tibia and around the resection line or bone defect in a 3-dimensional collagen sponge scaffold. After the MSC transplantation, the patients were monitored during a 10-month follow-up period. In both cases, bone formation at the pseudarthrosis site was observed and two of three treated bone defects healed. For clinical reasons not related to cell transplantation, such as new infection and pseudarthrosis and severe shortening of the leg, both extremities were finally amputated and bone samples were analyzed to evaluate MSC therapy effect and safety.


RESULTS
MSC transplantation normalized bone remodeling, promoted bone resorption and improved the overall structure of bone. The number of osteoclasts in the cortical bone was 2-fold higher compared with the monitored situation before MSC transfer. In addition, the mineral content of the bone improved after transplantation. We could see no sign of aberrant bone formation or malignant transformation.


CONCLUSIONS
Our data suggest that MSC transplantation is a possibility for treatment of CPT caused by NF1 in less severe cases without adjunct defects.
Tikkanen
Jonne
J
Department of Surgery, Clinical Research Center, Oulu University Hospital, Oulu, Finland. jonne.tikkanen@oulu.fi
Leskelä
Hannu-Ville
HV
Lehtonen
Siri T
ST
Vähäsarja
Vesa
V
Melkko
Jukka
J
Ahvenjärvi
Lauri
L
Pääkkö
Eija
E
Väänänen
Kalervo
K
Lehenkari
Petri
P
D001853:Bone Marrow / Q000473:pathology*; D016723:Bone Remodeling; D002113:Calcification, Physiologic; D002478:Cells, Cultured; D002648:Child; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009456:Neurofibromatosis 1 / Q000235:genetics / Q000503:physiopathology; D010012:Osteogenesis; D011542:Pseudarthrosis / Q000151:congenital / Q000503:physiopathology / Q000628:therapy*; D017154:Stromal Cells / Q000166:cytology / Q000637:transplantation; D013977:Tibia / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D054457:Tissue Scaffolds