Pre-clinical safety testing supporting clinical use of allogeneic multipotent adult progenitor cells

M. Kovacsovics-Bankowski, K. Mauch, A. Raber, Philip Streeter, R. J. Deans, Richard Maziarz, W. Van't Hof

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background: Successful clinical development of novel cellular therapeutics requires the evaluation of clinical acute toxicity endpoints in scoring patient adverse events (AE) contributing to dose-limiting toxicity (DLT) for establishment of the maximum-tolerated dose (MTD). However, many clinical pathology parameters are not routinely evaluated in pre-clinical safety testing. The objective of this pre-clinical study was to investigate thoroughly the acute toxicity of single- and multiple-dose administrations of allogeneic multipotent adult progenitor cells (MultiStem®), which represent a class of stromal stem cells with therapeutic potential. Methods: MultiStem were tested as an adjunct treatment in a rat myeloablative hematopoietic stem cell transplantation (HSCT) model for impact on clinical parameters, clinical chemistry, hematology, immunology and histopathology parameters. Animals received MultiStem in a single dose of 12.5 million cells/kg on day 2 after HSCT or in five infusions at this dose on days 2, 9, 16, 23 and 30. Controls received phosphate-buffered saline injections and all animals were killed on day 37. Results: There were no significant differences between tests and controls regarding evaluation of respiratory distress upon infusion, clinical assessment and hematology and clinical chemistry analysis. Gross necropsy and histopathology analysis showed no organ profile alterations. There was no significant evidence for allogeneic antibody production or T-cell sensitization upon MultiStem infusion. Discussion: These studies demonstrate the safety of administration of allogeneic stromal stem cells in repeat dosing regimens in bone marrow transplant settings, and define pre-clinical safety testing standards relevant to the development of cellular therapeutics using allogeneic adherent adult stem cells.

Original languageEnglish (US)
Pages (from-to)730-742
Number of pages13
JournalCytotherapy
Volume10
Issue number7
DOIs
StatePublished - 2008

Fingerprint

Stem Cells
Safety
Clinical Chemistry
Hematopoietic Stem Cell Transplantation
Hematology
Stromal Cells
Adult Stem Cells
Clinical Pathology
Maximum Tolerated Dose
Therapeutics
Allergy and Immunology
Antibody Formation
Bone Marrow
Phosphates
T-Lymphocytes
Transplants
Injections

Keywords

  • Bone marrow
  • Cell therapy
  • Pre-clinical
  • Safety evaluation
  • Stem cell
  • Transplantation

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Molecular Medicine

Cite this

Kovacsovics-Bankowski, M., Mauch, K., Raber, A., Streeter, P., Deans, R. J., Maziarz, R., & Van't Hof, W. (2008). Pre-clinical safety testing supporting clinical use of allogeneic multipotent adult progenitor cells. Cytotherapy, 10(7), 730-742. https://doi.org/10.1080/14653240802320245

Pre-clinical safety testing supporting clinical use of allogeneic multipotent adult progenitor cells. / Kovacsovics-Bankowski, M.; Mauch, K.; Raber, A.; Streeter, Philip; Deans, R. J.; Maziarz, Richard; Van't Hof, W.

In: Cytotherapy, Vol. 10, No. 7, 2008, p. 730-742.

Research output: Contribution to journalArticle

Kovacsovics-Bankowski, M, Mauch, K, Raber, A, Streeter, P, Deans, RJ, Maziarz, R & Van't Hof, W 2008, 'Pre-clinical safety testing supporting clinical use of allogeneic multipotent adult progenitor cells', Cytotherapy, vol. 10, no. 7, pp. 730-742. https://doi.org/10.1080/14653240802320245
Kovacsovics-Bankowski, M. ; Mauch, K. ; Raber, A. ; Streeter, Philip ; Deans, R. J. ; Maziarz, Richard ; Van't Hof, W. / Pre-clinical safety testing supporting clinical use of allogeneic multipotent adult progenitor cells. In: Cytotherapy. 2008 ; Vol. 10, No. 7. pp. 730-742.
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