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Regenerative medicine using bone marrow-derived mesenchymal cells and platelet-rich plasma for maxillomandibular bone defect (TEOM)

Tissue-Engineered Osteogenic Material for maxillomandibular bone defect (TEOM)

Kodera Yasuhiro

April. 13, 2022

4

Bone marrow-derived mesenchymal cells (BM-MSC) group (n=3) / Control group Sex: female 100% / female 100% Age: 40.0+/-23.1 / 39 Body weight: 52.1+/-6.2 kg / 40.8 kg Reason for maxillomandibular bone defect: tumor removal 67%, maxillofacial injury 33% / tumor removal 100% Bone augmentation history: Yes 33% / Yes 100% Number of predetermined region for regeneration: less than 4 33%, 5 or 6 33%, more than 7 33% / more than 7 100%

BM-MSC group: n=3, 17 regions Control group: n=1, 11 regions

Safety analysis was carried out for the 4 enrolled patients, and there was no fatal event. Serious adverse events were encountered in one patient, including medical device site infection and histology abnormal. All patients suffered any adverse events. postoperative wound complication and procedural pain were encountered in more than 2 patients of in this study. Histology abnormal in one patient was related to mixture of regenerative cells. Oral infection was occurred in one patient. There was no problematic change in laboratory test.

The FAS included 4 patients who underwent transplantation of mixture of regenerative cells and provided the data after administration. Primary endpoint The rate of implanted sites with successful bone augmentation [95% CI]: BM-MSC group 14/17 sites, 82.4% [56.6%, 96.2%] / Control group 10/11 sites, 90.9% [58.7%, 99.8%] Secondary endpoint 1) Regenerated bone height by facial CT (mean+/-SD): BM-MSC group 12.71+/-5.73mm / Control group 6.42+/-2.62mm at 6 months, BM-MSC group 11.71+/-5.16mm / Control group 5.41+/-2.59mm at 12 months, BM-MSC group11.40+/-5.88mm / Control group 3.44+/-3.17mm at 24 months 2) Percentage of the regenerated bone height over the height of the initial defect by facial CT: BM-MSC group 169.13+/-122.49% / Control group 47.57+/-10.87% at 6 months, BM-MSC group 155.09+/-105.21% / Control group 39.79+/-13.24% at 12 months, BM-MSC group 151.47+/-124.54% / Control group 19.07+/-28.66% at 24 months 3) CT value: BM-MSC group 634.18+/-192.36 / Control group 267.49+/-119.98 at 6 months, BM-MSC group 639.36+/-243.25 / Control group 407.70+/-145.32 at 12 months, BM-MSC group 814.91+/-177.21 / Control group 549.25+/-192.33 at 24 months 4) Rate of successful implant placement: BM-MSC group 4/9 sites, 44.4% [13.7%, 78.8%] / Control group 2/2 sites, 100.0% [15.8%, 100.0%] 5) Time from transplantation to implant placement (median): BM-MSC group 413 days / Control group 422 days 6) Survival rate and time of dental implant: BM-MSC group 100.0% [39.8%, 100.0%] / Control group 100.0% [15.8%, 100.0%]

We could not enrolled patients with predetermined defect sites, therefore, we could not achieve main purpose of this clinical research. Although it is not possible to fully discuss about the efficacy of this mixture of regenerative cells based on this incompleted study, it seems to be short of number of cells in case of large defect, because no clear improvement in bone regeneration was observed in the BM-MSC group.

Oct. 30, 2023

No

Data on individual subjects obtained in this clinical trial will not be disclosed at this time for the protection of personal information, because the risk of 're-identification' is high due to small number of enrolled patients.

https://jrct.mhlw.go.jp/latest-detail/jRCTb041190076

Okabe Kazuto

Nagoya University

65 Tsurumai-cho, Showa-ku, Nagoya, Aichi

kokabe@med.nagoya-u.ac.jp

Shimizu Shinobu

Nagoya University

65 Tsurumai-cho, Showa-ku, Nagoya, Aichi

+81-52-744-2942

teom-study@med.nagoya-u.ac.jp

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

1. Patients who require bone regeneration satisfying all of the inclusion criteria below:
more than 20-year-old patients who have a maxillomandibular bone defect that lies over 1/3 of the maxillomandibular area with remaining bone of up to 10 mm in height due to maxillofacial injury or tumor/cyst removal (Patients who had surgical tumor removal in maxillomandibular region must not have relapse/metastasis for 5 year of observation period after the procedure)
2. Patients who have received plaque control instructions by a dentist or a dental hygienist and are in a good management of it
3. Patients who are willing and able to give signed consent

1. Patients with bone defect as a result of periodontitis
2. Patients for whom surgical procedure is prohibited e.g, severe heart disease, congenital coagulation factor deficiency, leukemia, dialysis, end-stage malignant tumor
3. Patients with or with a history of infection
4. Patients with diabetes that is not well-controlled
5. Patients taking bisphosphonates for more than 3 months or denosumab for more than 6 months before the consent
6. Patients with or with a history of malignant tumor
7. Patients taking steroids or immunosuppressive drugs who cannot stop such medication for 4 weeks after trial intervention
8. Patients in a serious condition of certain diseases
9. Patients with difficulty in bone marrow aspiration
10. Patients from whom a sufficient amount of blood cannot be taken for PRP preparation
11. Patients with contraindications to local anesthetics
12. Patients with a history of hypersensitivity to antibiotics, antifungals, thrombin products, or bovine blood-derived products
13. Patients taking hemocoagulase products, tranexamic acid products, or aprotinin products
14. Female patients who are pregnant, suspected to be pregnant, breastfeeding, or those who do not agree to practice contraception
15. Any other patients whom the trial investigator deemed ineligible to this study

Both

maxillomandibular bone defect

Cell transplantation

Cell transplantation

Transplantation of bone marrow-derived mesenchymal cells, platelet rich plasma, thrombin, calcium chloride and beta-TCP

abnormality, maxillofacial

maxillomandibular bone defect

Rate of procedure sites with successful bone regeneration

1) Regenerated bone height
2) Percentage of the regenerated bone height over the height of the initial defect
3) CT value
4) Rate of successful implant placement
5) Time from transplantation to implant placement
6) Survival rate and time of implant
7) Tooth mobility
8) Masticatory force
9) Histological assessment

Complete

+81-52-744-2479

July. 28, 2015