Review Article

Clinical Application of Human Mesenchymal Stromal Cells for Bone Tissue Engineering

Table 1

Overview of the clinical studies performed on humans using-tissue engineered constructs.

Principal investigatorYearCell sourceScaffoldPatientsArea of reconstructionSalient featuresEvaluationReported outcome

R.Quarto2001Bone marrow100% hydroxyapatite3Long bone defects (1 tibia, 1 ulna, 1 humerus)(1) First clinical trial in humans using hMSCs
(2) Patients with long bone defects selected
(3) Patients had good clinical recovery
(3) No side effects even after 6-7 years followup
Radiology CT scan AngiographyNo quantification of new bone formed.
Good integration of the host bone with the implanted scaffolds

H. Hibi2006Bone marrowPlatelet gel1Alveolar cleft defect(1) First study using platelet gel as the scaffolding materialSerial Ct scansComparable bone formation to that described in literature with autolgous bone grafts

Y.Soleymani2007 Bone marrow HA/TCP6 Maxillary sinus augmentation (1) Good bone formation in all scaffolds
(2) Mean amount of new bone regenerated was 41.3%
(3) When compared to the Vacnati study, stark difference in the amount fo bone formed, probably due to location of defect or cell source
Radiology Biopsy Reported successful with mean bone regenerate as 41.34% and good osseointegration

H.Krecic-Stres2007Bone marrowPorous calcium triphosphate granules1Femoral defect (1) autologous bone graft was mixed with TECs made with MSCs and scaffolds in ratio of 1 : 2 to fill the defectRadiologyGood clinical recovery. No bone quantification performed

Gert Meijer2008Bone marrow Hydroxyapatite scaffolds6 Intraoral osseous defects(1) Only study which performed a biopsy to not just to quantify the amount of bone formed but also the location of bone on the scaffold.
This helped identify if the bone was formed due to osteoconduction alone or as a result of osteo conduction with de novo bone sytnthesis.
(2) Demonstarted the donor donor variation with hMSCs
Radiology Biopsy5 patients had no new bone

K. Mesimaki2009Adipose tissueβ-TCP1Maxillary reconstruction(1) First clinical study to use autologous MSCs derived from adipose tissue and expanded employing good manufacturing protocols (GMP) to heal a bone defect.
(2) Use of rhBMP-2 to promote bone formation in vivo.
(3) Use of a microvascular flap reconstruction surgery for bone tissue engineering
Radiology biopsy8-month followup indicated presence of mature bone. No quantification of the amount of bone formed is provided.
Good clinical course

Jun Lee2010Bone marrowFreeze dried Autologous cancellous bone1Mandible reconstruction(1) Repair of a large segmental defect (15 cm)
(2) Injection of MSCs with fibrin glue into the defect site.
(3) Use of autologous cancellous freeze dried bone as a tray to hold the MSCs in place.
Biopsy radiologyNew bone formation after 4 months.
No quantification provided.
Goo clinical recovery