Table 1.
Clinical studies using MSCs and isolated progenitors for bone regeneration.
| Identifier | Phase | Completion | Condition | Cell type | Patients | Treatment groups | Masking | Main outcome (Reference) |
|---|---|---|---|---|---|---|---|---|
| SEARCH TERMS: “BONE FRACTURE, STEM CELLS” | ||||||||
| NCT03325504 | III | Recruiting | Non-union | Autologous bone marrow MSCs (in vitro expanded) | Est. 108 | Low dose stem cell application with biomaterial High dose stem cell application with biomaterial Control autologous bone graft |
None | / |
| NCT02483364 | II | Recruiting | Pseudoarthrosis | Autologous or allogeneic adipose MSCs | Est. 12 | Allogeneic stem cell application with tricalcium phosphate Autologous stem cell application with tricalcium phosphate |
None | / |
| NCT02815423 | I/II | Not yet recruiting | Non-union | Umbilical cord MSCs | Est. 40 | Stem cell injection Control placebo injection |
None | / |
| NCT01842477 | I/II | February 2016 | Delayed union Non-union |
Autologous bone marrow MSCs (cultured) | 30 | Application of stem cells with bone substitute | None | No severe adverse events and 26/28 treated patients radiologically healed at 1 year (Gómez-Barrena et al., 2019) |
| NCT01813188 | II | December 2013 | Pseudoarthrosis | Autologous bone marrow MNCs | 5 | Application of cells seeded on tricalcium phosphate | None | / |
| NCT01788059 | II | November 2013 | Non-union | Autologous bone marrow MSCs (Ficoll separated) | 19 | Stem cell injection | None | / |
| NCT01581892 | I/II | January 2013 | Non-union | Autologous bone marrow MNCs (Ficoll separated) | 7 | Stem cell injection | None | / |
| NCT02177565 | NA | October 2011 | Non-union | Autologous bone marrow MSCs (in vitro expanded) | 35 | Stem cell application with carrier Control carrier alone |
Double | / |
| NCT01206179 | I | March 2011 | Non-union | Autologous bone marrow MSCs (in vitro expanded) | 6 | Stem cell injection | None | Stem cell injections were tolerated with evidence of union in 3/5 patients (Emadedin et al., 2017) |
| NCT00916981 | I/II | June 2009 | Non-union Pseudoarthrosis |
Autologous bone marrow derived pre-osteoblastic cells | 30 | Pre-osteoblastic cell injection | None | / |
| NCT02140528 | II | April 2016 | Tibial fracture | Allogeneic adipose MSCs | 40 | Stem cell injection Control placebo injection |
Double | / |
| NCT00512434 | NA | September 2013 | Tibial fracture, open fracture | Autologous bone marrow MNCs | 85 | Stem cell injection and osteosynthesis Control osteosynthesis only |
None | / |
| NCT00250302 | I/II | April 2011 | Tibial fracture | Autologous bone marrow MSCs (isolated) | 24 | Stem cell implantation with autologous platelet rich plasma/demineralized bone carrier Control no treatment |
None | Shorter time to union in stem cell group (1.5 months) compared to control group (3 months) (Liebergall et al., 2013) |
| NCT02755922 | III | December 2010 | Mandibular fracture | Autologous adipose MSCs (24 h post-isolation) | 20 | Stem cell application Control no application |
Single | Ossification values in stem cell group were similar to control at 4 weeks and higher as control at 12 weeks (Castillo-Cardiel et al., 2017) |
| NCT01532076 | III | September 2014 (terminated) | Osteoporotic fracture | Autologous stromal vascular fraction | 8 | Application of cell-seeded hydroxyapatite/fibrin gel graft Control acellular composite graft |
Single | / |
| SEARCH TERMS: “BONE, STEM CELLS, MAXILLA, ALVEOLAR” | ||||||||
| NCT03766217 | III | Not yet recruiting | Cleft lip and palate | Autologous MSCs from deciduous dental pulp (enzyme isolated) | Est. 62 | Application of stem cells with collagen and hydroxyapatite Control autologous bone graft |
None | / |
| NCT02751125 | I | Recruiting by invitation | Bone atrophy | Autologous bone marrow MSCs (cultured) | 13 | Application of stem cells mixed with biphasic calcium phosphate | None | Treatment resulted in bone formation sufficient for dental implant placement after 4–6 months (Gjerde et al., 2018) |
| NCT03070275 | I/II | December 2017 | Implant therapy | Autologous alveolar bone marrow MSCs (in vitro expanded) | 20 | Application of stem cells with autologous fibrin glue in collagen scaffold | Single | / |
| NCT02449005 | I/II | December 2016 | Chronic periodontitis | Autologous alveolar bone marrow MSCs (in vitro expanded) | 30 | Application of stem cells with autologous fibrin glue in collagen scaffold Control fibrin glue with collagen scaffold alone Control no graft materials |
Quadruple | / |
| NCT01389661 | I/II | April 2016 | Maxillary cyst Bone loss of substance | Autologous jaw bone marrow MSCs (cultured, pre-differentiated in osteogenic matrix) | 11 | Application of cells cultured in autologous plasma matrix | None | Treatment resulted in increased cyst density by CT and no adverse effects (Redondo et al., 2018) |
| NCT02859025 | I | February 2016 | Cleft of alveolar ridge | Autologous buccal fat pad MSCs (cultured on bovine bone mineral) | 10 | Cells cultured on bovine bone applied with autologous spongy bone and collagen membrane Cells cultured on bovine bone applied with autologous cortical bone Control autologous spongy bone with collagen membrane |
None | Cell-therapy groups showed a trend of higher bone formation after 6 months (Khojasteh et al., 2017) |
| NCT01932164 | NA | December 2015 | Cleft lip and palate | Autologous MSCs from deciduous dental pulp (isolated, characterized, frozen) | 5 | Application of stem cells with collagen and hydroxyapatite | None | Bone formation closing the alveolar cleft after 6 months in all patients |
| SEARCH TERMS: “OSTEONECROSIS, STEM CELLS” | ||||||||
| NCT02448121 | I/II | Active, not recruiting | Avascular necrosis of bone in sickle cell disease patients | Autologous bone marrow MNCs | Est. 100 | Stem cell injection | None | / |
| NCT01605383 | I/II | Active, not recruiting | Avascular necrosis of the femoral head | Autologous bone marrow MSCs (cultured) | Est. 24 | Application of cells with allogeneic bone Control standard treatment only |
None | / |
| NCT02065167 | II | Active, not recruiting | Avascular necrosis of the femoral head | Autologous bone marrow MSCs (cultured) | 26 | Stem cell injection | None | / |
| NCT01700920 | II | December 2015 | Osteonecrosis of the femoral head | Autologous bone marrow MSCs (cultured) | 3 | Stem cell injection | None | / |
| NCT01643655 | NA | March 2015 | Avascular necrosis of the femoral head | Autologous adipose MSCs | 15 | Stem cell injection | None | / |
| NCT01198080 | I | June 2013 | Osteonecrosis of the femoral head | Autologous CD133 bone marrow cells | 10 | Stem cell injection | None | Treatment resulted in disease score improvement, reduced joint injuries and pain relief (Emadedin et al., 2019) |
| NCT01544712 | NA | September 2010 | Osteonecrosis of the femoral head | Autologous bone marrow aspirate concentrate | 50 | Bone marrow concentrate injection Control standard treatment only |
Double | Cell therapy did not improve stage 3 osteonecrosis (Hauzeur et al., 2018) |
| NCT00821470 | I | September 2008 | Osteonecrosis of the femoral head | Autologous bone marrow aspirate | 21 | Bone marrow injection Control standard treatment only |
Triple | / |
Studies were searched in the Clinicaltrials.gov database (July 2019), using combinations of search terms “bone, bone fracture, stem cells, maxilla, alveolar, osteonecrosis.” Registered studies with unknown status and terminated studies were excluded. Cell type designation in the table is according to the information provided for the specific clinical study in the database.