Analysis of the Karyotype of Expanded Human Adipose-Derived Stem Cells for Bone Reconstruction of the Maxillo-Facial Region

C. Bellotti, D. Stanco, S. Ragazzini, L. Romagnoli, E. Martella, S. Lazzati, C. Marchetti, D. Donati, E. Lucarelli

Research output: Contribution to journalArticle

Abstract

Mesenchymal stem cells (MSC) and adipose-derived stem cells (ASC) were recently proposed for bone maxillo-facial reconstruction in association with biomaterials. For this application MSC must be ex-vivo expanded in order to obtain, for a given volume of implanted biomaterial, a relevant number of bone forming cells. Previously conducted pre-clinical studies suggested that a concentration of 6 × 108 ASC associated with 900 mg of anorganic bovine bone (ABB) could be effective for human maxillary sinus floor elevation. A keystone issue to guarantee the quality and safety of Advanced Therapy Medicinal Products containing expanded MSC and ASC is their chromosome stability in culture: this topic has been widely investigated and conflicting results have been published. Abnormal karyotype of human ex-vivo expanded MSC and ASC was found by some authors, while, at the same time, several other studies showed the MSC and ASC karyotype to be normal. It is therefore important that all the results obtained on MSC and ASC karyotype analysis be published. Given this context, the aim of this manuscript, aim of this manuscript is to verify the karyotype stability of ASC in view of their applications in clinical trials. ASC obtained from the adipose tissue of 4 donors were expanded over extended culture time. Based on previous ASC expansions we hypothesized to be able to obtain 6 × 108 cells by passage 7. Karyotype analysis of 30 metaphases was planned to be investigated at passage 2, 7, and 15 in all the cultures. No abnormalities were found in the karyotype of two donors at all the passages tested, while a translocation was found in 2 metaphases of a donor at passage 7, but not at passage 15, and in the fourth donor in 5 metaphases a trisomy was found at passage 15. Chromosomal abnormalities were detected only after extended ASC expansion. Whether these anomalies can be related to risk for the patient's safety will have to be demonstrated by in-vivo studies.

Original languageEnglish
Pages (from-to)3-9
Number of pages7
JournalInternational Journal of Immunopathology and Pharmacology
Volume26
DOIs
Publication statusPublished - Jan 1 2013

Fingerprint

Karyotype
Stem Cells
Bone and Bones
Mesenchymal Stromal Cells
Metaphase
Biocompatible Materials
Facial Bones
Abnormal Karyotype
Chromosomal Instability
Maxillary Sinus
Trisomy
Patient Safety
Chromosome Aberrations
Adipose Tissue
Tissue Donors
Clinical Trials
Safety

Keywords

  • adipose-derived stem cells
  • bone
  • cytogenetic analysis
  • maxillo-facial reconstruction

ASJC Scopus subject areas

  • Pharmacology
  • Immunology
  • Immunology and Allergy

Cite this

Analysis of the Karyotype of Expanded Human Adipose-Derived Stem Cells for Bone Reconstruction of the Maxillo-Facial Region. / Bellotti, C.; Stanco, D.; Ragazzini, S.; Romagnoli, L.; Martella, E.; Lazzati, S.; Marchetti, C.; Donati, D.; Lucarelli, E.

In: International Journal of Immunopathology and Pharmacology, Vol. 26, 01.01.2013, p. 3-9.

Research output: Contribution to journalArticle

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