Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
Toxicologic Pathology
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
0192623309338383v1
37/5/606    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Ramot, Y.
Right arrow Articles by Nyska, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ramot, Y.
Right arrow Articles by Nyska, A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Articles

Safety and Biodistribution Profile of Placental-derived Mesenchymal Stromal Cells (PLX-PAD) Following Intramuscular Delivery

Yuval Ramot1
Moran Meiron2
Amir Toren2
Michal Steiner3
Abraham Nyska4

1 Hadassah–Hebrew University Medical Center, Jerusalem, Israel
2 Pluristem Therapeutics, Inc., Haifa, Israel
3 Harlan Biotech Israel Ltd., Rehovot, Israel
4 Consultant in Toxicological Pathology, Sackler School of Medicine, Tel Aviv University, Israel

Correspondence: Address correspondence to: Abraham Nyska, D.V.M., Dipl. ECVP, Haharuv 18, P.O. Box 184, Timrat, Israel 36576; e-mail:anyska{at}bezeqint.net.

The administration of mesenchymal stromal cells (MSCs) provides an exciting emerging therapeutic modality for the treatment of peripheral arterial disease, a condition that is associated with critical limb ischemia as its end stage. Placental-derived MSCs, termed PLX-PAD cells, are stable adhesive stromal cells isolated from full-term human placentae, cultured on carriers, and expanded in a bioreactor called the PluriX. These cells can be expanded in vitro without phenotypic or karyotypic changes. We studied the safety and biodistribution properties of PLX-PAD cells following intramuscular administration in NOD/SCID mice. No significant clinical signs, hematological and biochemical parameters, or major pathological changes were found in PLX-PAD-treated animals in comparison to vehicle controls. Several animals in the control and PLX-PAD-treated groups developed thymic malignant lymphoma, first seen after one month, as expected in this mouse strain. In addition, both groups developed spontaneous mesenteric vessel inflammation. Real-time quantitative polymerase chain reaction (RT-qPCR) demonstrated that distribution of PLX-PAD cells was confined to the injection site. Placental-derived MSCs remained in this site with gradual decrease in concentration during a three-month period. In view of these data, we conclude that the administration of PLX-PAD cells is not associated with any adverse effects in NOD/SCID mice.

Key Words: limb ischemia • bone marrow transplant • safety profile • biodistribution • PLX-PAD

Abbreviations: 2DCS, 2D-Cell Stock • CLI, critical limb ischemia • IM, intramuscular • MSC, mesenchymal stromal cell • NOD/SCID, nonobese diabetic/severe combined immunodeficient • PAD, peripheral arterial disease • RT-qPCR, real-time quantitative polymerase chain reaction

This version was published on August 1, 2009

Toxicologic Pathology, Vol. 37, No. 5, 606-616 (2009)
DOI: 10.1177/0192623309338383
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?