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

Stem Cells Transl Med. 2021 Apr;10(4):554-567. doi: 10.1002/sctm.20-0308. Epub 2020 Dec 16.

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 × 107 cells] injection and intravenous [2 × 108 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.

Keywords: Wharton's jelly; mesenchymal stem cells; osteoporosis; teriparatide; vertebral compression fracture.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Density
  • Bone Density Conservation Agents* / therapeutic use
  • Fractures, Compression* / therapy
  • Humans
  • Mesenchymal Stem Cell Transplantation*
  • Osteoporotic Fractures / therapy*
  • Spinal Fractures* / therapy
  • Teriparatide* / therapeutic use
  • Wharton Jelly* / cytology

Substances

  • Bone Density Conservation Agents
  • Teriparatide