Safety and efficacy of Wharton's jelly-derived mesenchymal stem cells with teriparatide for osteoporotic vertebral fractures: A phase I/IIa study

Abstract

Osteoporotic vertebral compression fractures (OVCFs) are serious health problems. We conducted a randomized, open-label, phase I/IIa study to determine the feasibility, safety, and effectiveness of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) and teriparatide (parathyroid hormone 1-34) in OVCFs. Twenty subjects with recent OVCFs were randomized to teriparatide (20 μg/day, daily subcutaneous injection for 6 months) treatment alone or combined treatment of WJ-MSCs (intramedullary [4 × 10 7 cells] injection and intravenous [2 × 10 8 cells] injection after 1 week) and teriparatide (20 μg/day, daily subcutaneous injection for 6 months). Fourteen subjects (teriparatide alone, n = 7; combined treatment, n = 7) completed follow-up assessment (visual analog scale [VAS], Oswestry Disability Index [ODI], Short Form-36 [SF-36], bone mineral density [BMD], bone turnover measured by osteocalcin and C-terminal telopeptide of type 1 collagen, dual-energy x-ray absorptiometry [DXA], computed tomography [CT]). Our results show that (a) combined treatment with WJ-MSCs and teriparatide is feasible and tolerable for the patients with OVCFs; (b) the mean VAS, ODI, and SF-36 scores significantly improved in the combined treatment group; (c) the level of bone turnover markers were not significantly different between the two groups; (d) BMD T-scores of spine and hip by DXA increased in both control and experimental groups without a statistical difference; and (e) baseline spine CT images and follow-up CT images at 6 and 12 months showed better microarchitecture in the combined treatment group. Our results indicate that combined treatment of WJ-MSCs and teriparatide is feasible and tolerable and has a clinical benefit for fracture healing by promoting bone architecture. Clinical trial registration: https://nedrug.mfds.go.kr/, MFDS: 201600282-30937.

CD317-Positive Immune Stromal Cells in Human “Mesenchymal Stem Cell” Populations

“…The majority of trials assessing efficacy of MSCs currently aim to harness immunomodulatory properties ( 10 ), though widespread clinical translation is greatly hindered by insufficient data demonstrating strong and consistent clinical effect, mechanisms of action and diverse application of selection criteria ( 11 ). In addition, MSCs from different origins have been applied in clinical trials with varied outcomes for disorders including osteoarthritis ( 12 – 15 ), osteoporotic fracture repair ( 16 ), rheumatoid arthritis ( 17 – 19 ), type 1 diabetes mellitus ( 20 ), diabetic kidney disease ( 21 ), multiple sclerosis ( 22 , 23 ), liver failure ( 24 – 26 ), amyotrophic lateral sclerosis ( 27 – 30 ) and COVID-19 ( 31 – 33 ). Notably, although serious adverse events are extremely rare, mild, transient or acute adverse events occurring are often related to acute inflammation ( 13 – 16 , 19 , 21 , 25 , 29 , 30 ), fever (pyrexia) ( 17 , 19 , 22 , 24 , 26 , 30 , 34 ), infection ( 12 , 16 , 21 , 23 , 30 ), allergic reactions/hypersensitivity ( 13 , 15 , 16 , 19 ) and hematoma ( 13 ), all of which are implicated in immune responses.…”

Umbilical Cord-Derived Wharton’s Jelly for Regenerative Medicine Applications: A Systematic Review

“…Bone mineral density improved significantly for both the control and experimental groups, but there was no statistically significant difference between the two groups. CT analysis demonstrated an improved microarchitecture for the experimental group compared to the control group at 12 months [25].…”

Clinical application of mesenchymal stem cell in regenerative medicine: a narrative review

“…MSC Decreased WOMAC score NCT03800810 [ 127 ] Bone fracture Percutaneous 22 50–100 × 10 6 cell BMSC I/II No TUS, GDE score was improved and pain at palpation at the fracture site was reduced NCT02020590 [ 128 ] Bone fracture Intramedullary I.V 20 4 × 10 7 cells 2 × 10 8 cells WJ-MSC I/IIa No VAS, ODI, and SF-36 scores significantly improved. Promoted bone architecture N/A [ 129 ] Mandibular lesions Intralesional 20 N/A BMSC N/A No Increase in bone density with respect to the baseline levels. The percent of reduction in the defects’ size was significantly higher compared with control N/A [ 130 ] Wound healing Intralesional 8 1 × 10 6 cell BMSC N/A No Reduction in ulcer size or complete wound closure N/A [ 131 ] Wound healing N/A 316 N/A Adipose MSC N/A No Granulation tissue coverage rate and thickness of granulation tissue were significantly improved N/A …”