Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report

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Summary

This is a report of a 7-year-old girl suffering from widespread calvarial defects after severe head injury with multifragment calvarial fractures, decompressive craniectomy for refractory intracranial hypertension and replantation of cryopreserved skull fragments. Chronic infection resulted in an unstable skull with marked bony defects. Two years after the initial injury the calvarial defects were repaired. Due to the limited amount of autologous cancellous bone available from the iliac crest, autologous adipose derived stem cells were processed simultaneously and applied to the calvarial defects in a single operative procedure. The stem cells were kept in place using autologous fibrin glue. Mechanical fixation was achieved by two large, resorbable macroporous sheets acting as a soft tissue barrier at the same time. The postoperative course was uneventful and CT-scans showed new bone formation and near complete calvarial continuity three months after the reconstruction.

Introduction

Several procedures have been described for reconstructing the skull (bones). Most commonly, split thickness calvarial bone grafts have been used with good success (Goodrich et al., 1992; Inoue et al., 1995; Barone and Jimenez, 1997). Bone substitutes such as hydroxyapatite cement (e.g. BoneSourceTM) or methylmethacrylates (e.g. PalacosTM) have also been recommended (Lew et al., 1997; Friedman et al., 2000; Eppley et al., 2003; Chiarini et al., 2004). Individual prefabricated titanium implants using CAD/CAM techniques are also described for reconstructing the skull (Joffe et al., 1999; Eufinger and Wehmöller, 2002). Nevertheless, it is widely accepted that autogenous bone grafts currently are the best material for bony reconstruction in craniofacial surgery, especially in children (Tatum and Kellmann, 1998; Bussieres and Tatum, 2000; Lenz et al., 2003).

However, in children, successful repair of large skull defects is often difficult because of the limited amount of autogenous bone available. Accordingly, bone regeneration augmented by stem cells or osteoinductive proteins have been suggested (Langer and Vacanti, 1993; Boo et al., 2002; Park et al., 2003; Yamada et al., 2003). Most adult stem cell work has focused on mesenchymal stem cells from bone marrow. These have shown the potential to differentiate into adipocytes, chondrocytes, osteoblasts and myoblasts (Haynesworth et al., 1992; Bruder et al., 1997; Pittenger et al., 1999, Pittenger et al., 2000; Boo et al., 2002). However, harvesting adult stem cells from bone marrow yields low numbers of cells and may cause donor site morbidity (Ringe et al., 2002; Yamada et al., 2003).

Typically, cell culture is required to increase the number of stem cells. Zuk et al., (2002) recently reported that adipose tissue is an alternative source of multipotent stem cells. The stem cells are isolated from adipose tissue in large quantities and have shown stable growth and proliferation in vitro. They are also reported to be multipotent and can differentiate into various mesodermal tissues (e.g. fat, bone, cartilage and muscle) in vitro (Mizuno et al., 2002; Zuk et al., 2002; Dragoo et al., 2003; Lee et al., 2003).

Section snippets

Case report

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 °C (cryopreservation) for three weeks until secondary replantation and fixation was performed with titanium miniplates. Thereafter, progressive and disseminated calvarial bone resorption occurred over several months probably due to

Production of autologous fibrin glue

Two days prior to surgery the patient underwent plasmapheresis to obtain 315 ml of plasma. From this, autologous fibrin glue was manufactured following 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 (Gosselin et al., 1997; Rock et al., 2001

Discussion

In children, the repair of large skull defects may be difficult due to the limited amount of autogenous bone available. The use of alloplastic material is restricted to adults because of continuous calvarial growth in children. Hence the search for an alternative method of skull reconstruction in this patient.

Using autogenous stem cells for bone regeneration is a promising strategy (Langer and Vacanti, 1993; Yamada et al. 2003; Park et al. 2003). Until recently, only mesenchymal stem cells

Conclusion

We believe that this is the first report of the use of adipose derived stem cells to augment cancellous bone for the treatment of a difficult reconstructive problem. 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.

Acknowledgements

The authors wish to thank Joachim Misterek and Liesel Schindler-Wuepper from the Department of Clinical Immunology and Transfusion Medicine for their excellent technical assistance in processing the adipose derived stem cells. Furthermore, we are indebted to Dr. Detlef Kuhn, Department of Anaesthesiology, for his support in producing the autologous fibrin glue.

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