gms | German Medical Science

ESBS 2005: Skull Base Surgery: An Interdisciplinary Challenge
7. Kongress der Europäischen Schädelbasisgesellschaft & 13. Jahrestagung der Deutschen Gesellschaft für Schädelbasischirurgie

18. - 21.05.2005, Fulda

Osteoplasty in disseminated calvarial defects treated with autologous adipose derived stem cells and autologous fibrin glue: case report

Meeting Contribution

  • Stefan Lendeckel - Department of Maxillofacial and Facial Plastic Surgery, Justus-Liebig-University Medical School, Gießen, Germany
  • Andreas Jödicke - Department of Neurosurgery, Justus-Liebig-University Medical School, Gießen, Germany
  • Petros Christophis - Department of Neurosurgery, Justus-Liebig-University Medical School, Gießen, Germany
  • Kathrin Heidinger - Department of Clinical Immunology and Transfusion, Justus-Liebig-University Medical School, Gießen, Germany
  • Hans-Peter Howaldt - Department of Maxillofacial and Facial Plastic Surgery, Justus-Liebig-University Medical School, Gießen, Germany

ESBS 2005: Skull Base Surgery: An Interdisciplinary Challenge. 7th Congress of the European Skull Base Society held in association with the 13th Congress of the German Society of Skull Base Surgery. Fulda, 18.-21.05.2005. Düsseldorf: German Medical Science GMS Publishing House; 2009. Doc05esbs64

doi: 10.3205/05esbs64, urn:nbn:de:0183-05esbs644

Veröffentlicht: 27. Januar 2009

© 2009 Lendeckel et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction

Today reports about tissue engineering by stem cells or osteoinductive proteins are quite popular. Most adult stem cell work has focused on mesenchymal stem cells from bone marrow stroma.

However, harvesting adult stem cells from bone marrow stroma yields low numbers of cells and may cause donor site morbidity. Furthermore, ex vivo cell culture is required to increase the number of stem cells, which is time-consuming and expansive.

A scientific group from UCLA first reported that adipose tissue is an alternative source of adult stem cells. These adipose derived stem cells are isolated from adipose tissue in large quantities and have shown stable growth and proliferation in vitro. As MSC’s from bone marrow stroma, ADASC’s are reported to be multipotent and can also differentiate into various mesodermal tissues like fat, cartilage, muscle and bone in vitro.

In the presented case a 7-year-old girl sustained severe head injury resulting in a closed multifragment calvarial fracture after a fall. Because of refractory intracranial hypertension, a bilateral decompressive craniectomy had to be performed. Calvarial fragments were stored at 70 degrees below zero in cryopreservation for three weeks until secondary reimplantation and fixation was performed with miniplates.

Thereafter, progressive and disseminated calvarial bone resorption occurred. Almost all osteosynthesis plates loosened and ossification failed to appear at the sites of the former osteotomies. Subsequently, these resulted in an unstable skull, so the little girl was wearing a protective helmet.

Two years after the initial injury reconstruction were performed with the use of adipose derived stem cells, autologous fibrin glue and a limited amount of autogenous bone from the iliac crest.

Due to the ongoing chronic infection with significant bone resorption, an unstable skull and multiple surgical pretreatment procedures we had a difficult reconstructive problem.

Furthermore, because of the young age of the patient it was obvious that sufficient amount of autogenous bone material could not be harvested for a complete bony reconstruction of the calvaria. Therefore we used autologous adipose derived stem cells as well to enhance the regeneration process.

Case report

In an interdisciplinary surgical procedure, all osteosynthesis material and pseudarthrotic scar tissue were removed and an imprint with PalacosTM (as a template for resorbable sheet contouring) was created. Two resorbable macroporous sheets (Macropore PS Protective Sheet, Macropore, San Diego, USA), each measuring 10x20 cm and being 0,5 mm thick, were moulded in hot water to fit the PalacosTM imprint. Approximately 15 ml cancellous bone was taken from the ilium, milled and evenly applied to all bony defects (approximately 120 cm²). Thereafter, the premoulded protective sheets were fixed with resorbable tacks.

To enhance the regeneration process that was limited by the restricted amount of spongiosa, autologous adipose derived stem cells were applied as well. These cells were extracted from adipose tissue obtained from the gluteal region during harvesting of the dorsal iliac crest bone graft. Cell processing required two hours during the ongoing surgical procedure. Subsequently, 10 ml of the prepared solution of adipose stem cells were evenly injected through the holes of the protective sheets to soak the milled bone grafts. To keep the cells in place, 8 ml of autologous fibrin glue was applied using a spray adapter.

Material and method

Two days prior to surgery the patient underwent a plasmapheresis to obtain 315 ml of plasma for producing of fibrin glue. The autologous fibrin glue was manufactured following the methods of a standard cryoprecipitation procedure (CryoSeal® FS Systems, Thermogenesis, USA). The CryoSeal® FS System produces concentrated thrombin and the same amount of cryoprecipitate containing highly concentrated Factor VIII, Factor XIII, and fibrinogen from a single unit of autologous plasma in about one hour. Two syringes (4 ml each), one filled with sterile thrombin and one with sterile fibrinogen, were assembled in a dual syringe system, frozen –70°C, stored at –30°C and defrosted immediately prior to surgery.

A total amount of 42,3 g adipose tissue was excised from the left gluteal region during harvesting of the dorsal iliac crest bone graft, dissected into small pieces and transferred in the Department of Clinical Immunology and Transfusion Medicine. The adipose tissue was processed according to a standardized protocol in two hours only. The total number of extracted cells was 295 million mononuclear cells. About 2–3% of these cells can be expected to be stem cells.

Results

The postoperative course was uneventful. There were no neurological deficits. CT-scans showed marked new bone formation and near complete calvarial continuity three months after the repair.

Conclusions

In children, the repair of large skull defects is difficult due to the limited amount of autogenous bone available. The use of alloplastic material is restricted to adults because of ongoing calvarial growth. This is why it was looked for another way to reconstruct the skull in this patient.

In the present case, the total calvarial defect size was about 120 cm². It was obvious that sufficient amount of bone material could not easily be harvested for a complete bony reconstruction of the calvaria.

The use of autologous stem cells for bone regeneration opened a potent new therapeutic option. It was chosen to use adipose derived stem cells to enrich the limited amount of bone available for calvarial reconstruction. The milled cancellous bone served as an osteoconductive scaffold. Furthermore, fresh autologous milled cancellous bone contains growth factors and other cells which may stimulate the stem cells to differentiate into osteoblasts and osteocytes. To keep the stem cells in place, autologous fibrin glue was used.

The simultaneous stem cell transplantation together with bone harvesting and skull reconstruction in one surgical procedure was only made possible by an innovative processing protocol which made the stem cells available within 2 hours only.

Obviously, one cannot determine how much of the effect was due to the conventional bone graft versus that related to the combination of autologous adipose derived stem cell transplantation and autologous fibrin glue application.

Further studies, both in vitro and in vivo, are needed to turn this first case into a reproducible and reliable treatment regimen in craniofacial bone reconstruction.


References

1.
Lendeckel S, Jodicke A, Christophis P, Heidinger K, Wolff J, Fraser JK, Hedrick MH, Berthold L, Howaldt HP. Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report. J Craniomaxillofac Surg. 2004;32(6):370-3.