Table 3 Clinical studies of MSCs in the treatment of OI
From: Mesenchymal stem cells in the treatment of osteogenesis imperfecta
Type of OI | Cases | Treatment | Methods | Results | References |
|---|---|---|---|---|---|
III | 3 | Unmanipulated BM, HLA-identical or single-antigen mismatched siblings | IV, single infusion, moderate-dose total-body irradiation in mismatched donor | • Osteocytes decreased, osteoblasts increased • Increase in bone mineralization • Normalization of bone remodeling • Reduced fractures • ≤ 2% engraftment • Accelerated linear growth, but transient • 2/3 showed no toxicity | Womack 2014 |
• This is an extended follow-up of the above study • This study included 2 control patients • Evaluate patients up until 4 years of age • Growth rate immediately after treatment slowed, but mineralization increased • Decreased incidence of fractures remained | Yi et al. 2020 | ||||
III | 6 | Allogeneic BMSCs, Siblings or unrelated donors | IV, two infusions | • 5/6 patients showed engraftment of BMSCs @ 6 months • Engrafted in multiple tissues • Increased growth velocity @ 6 months • 1/6 had increased bone mineralization • No significant toxicity | Yu et al. 2021 |
III | 1 | Allogeneic HLA-mismateched FL-MSCs, 10-week male fetus Bisphosphonate treatments beginning at 4 months old | IUT 32 weeks gestation | • Engraftment was 7% at 9 months of age • Donor cells differentiated into bone cells • Mature trabecular • Minimal fractures within 2 years of age • Growth normal for child’s growth curve at 2 years of age • IUT of FL-MSCs was safe | Zhang et al. 2015 |
Booster from same FL-MSC donor | IV at 8 years old | • After 2 yrs. of age, growth rate decreased and fracture rate increased • Scoliosis developed • Donor cells not found in tissue @ 6 years of age • 9 months after booster, low engraftment levels found in bone • No fractures for two years after booster, growth velocity resumed • Ability to walk and participate in sports improved | Zhou et al. 2008 | ||
IV | 1 | Allogeneic HLA-mismateched FL-MSCs, 7-week male fetus | dose 1: IUT at 31 weeks, dose 2: IV at 19 months | • Low engraftment levels • Growth velocity plateaued ~ 12 months of age • Growth velocity increased after both injections | |
III and IV | 2 | HLA-haploidentical BMSCs from healthy siblings | 5 infusions, each 5-6 mo apart | TERCELOI Clinical Trial • No adverse effects with 5 treatments • Increased bone mineralization, trabecular thickness remained constant • Improved bone microstructure, but transient in severe patient • Reduced fractures • Treatment upregulated in sera: ECM, collagen binding, oxidoreductase activity, unsaturated fatty acid biosynthesis, osteogenic transcription factors • In sera, treatment downregulated: hypoxia, angiogenesis, collagen metabolic process, pro-adipogenic transcription factor | Yüksel Ülker et al. 2021 |
III | 1 (ongoing) | HLA-mismatched FL-MSCs | IV and IO | BOOST2B Clinical Trial (ongoing as of this publication) • Increase in growth velocity | Lazennec andet al. Jorgensen 2008 |
III, IV | ongoing | HLA-mismatched FL-MSCs | IUT and IV | BOOSTB4 Clinical Trial (ongoing) | Zhytnik et al. 2020 |