Co-transplantation of Umbilical Cord Tissue MSC’s to Improve Cord Blood Transplant Engraftment and reduced Graft vs Host Disease

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Co-transplantation of Umbilical Cord Tissue MSC’s to Improve Cord Blood Transplant Engraftment and reduced Graft vs Host Disease.

Exciting clinical work continues in the field of transplant medicine and mesenchymal stem cell therapy. Recent studies from China highlight the co-transplantation of umbilical cord mesenchymal stem cells (UC-MSC) and umbilical cord blood haematopoietic stem cells (CB-HSC).

These papers provide the first human data to support a scientific hypothesis suggested at the 7th International Cord Blood Society Congress in 2004. Researchers were already using bone marrow derived MSC’s to enhance HSC transplantation and therefore postulated that umbilical cord tissue MSC’s may be able to support haematopoiesis and enhance engraftment of the cord blood unit and several animal studies have supported this hypothesis.¹˒ ²˒³

These two Chinese studies used culture expanded MSC’s (perhaps native MSC’s may be more potent than culture expanded cells). They compared patients who were co-transplanted with UC-MSC and CB-HSC to patients transplanted with CB-HSC alone.  They showed that co-transplanted patients had significantly faster immune recovery and engraftment time (similar to that of a bone marrow transplant). This is a significant finding as cord blood transplants often take approximately 10 days longer to engraft than bone marrow stem cell transplants.⁴˒⁵

According to our present understanding bone marrow contains MSC’s, osteoblasts and other stromal cells (including sinusoidal and endothelial cells) that are responsible for supporting haematopoiesis and cord tissue contains similar cells. MSC’s have been shown to support in vivo haematopoiesis as well as displaying potent immune-suppressive effects.⁶

The mechanisms underlying their immunomodulatory action have not been fully elucidated but complex interactions with several immune cells such as natural killer cells, monocytes, dendritic cells and regulatory T cells are postulated. The four properties of MSc’s that are currently considered most important to their clinical uses are⁷:

1. Their ability to migrate to sites of inflammation following intravenous infusion

2.  Their ability to differentiate into various cell types

3. Their ability to secrete multiple bioactive molecules capable of inhibiting inflammation

4.  Their ability to perform immunomodulatory functions while lacking immunogenicity

MSC’s appear to be safe and well tolerated in cell therapy and are currently being investigated to treat patients with steroid-resistant Graft vs Host Disease (GVHD). Bone marrow MSC’s have been shown to be immune-suppressive but require invasive procedures to harvest them. Umbilical Cord MSC’s are harvested more easily and in one study showed superior proliferative potential and more suppressive effects than compared to bone marrow MSC.⁸

Hopefully these studies will pave the way for more extensive clinical trials using the combination of UC-MSC and CB-HSC in improving the outcomes of cord blood transplants.

Stem_cell_diagram
Stem_cells
Stem_cells

References:

1. Noort et al. Mesenchymal stem cells promote engraftment of human cord blood derived CD34(+) cells in NOD/SCID mice. Exp Hematol. 2002 Aug;30(8):870-8. Pubmed PMID: 12160838. (http://www.ncbi.nlm.nih.gov/pubmed/12160838)

2. Friedman R et al. Umbilical cord mesenchymal stem cells: adjuvants for human cell transplantation. Biol Blood Marrow Transplant.2007 Dec:13 (12): 1477-86. PubMed PMID: 18022578. (http://www.ncbi.nlm.nih.gov/pubmed/18022578)

3. Hiwase SD et al. Cotransplantation of placental Mesenchymal Stromal Cells Enhances Single and Double Cord Blood Engraftment in NOD/SCID mice. Stem Cells 2009;27: 2293-2300. doi: 10.1002/stem.157

4. Wu, KH et al. Cotransplantation of umbilical cord-derived mesenchymal stem cells promote hematopoietic engraftment in cord blood transplantation: a pilot stud. Transplantation. 2013 Mar 15, 95(5):773-7. doi: 10.1097/TP.0b013e31827a93dd. PubMed PMID:23274973. (http://www.ncbi.nlm.nih.gov/pubmed/23274973)

5. Wu KH et al. Human Application of Ex-vivo Expanded Umbilical Cord-Derived Mesenchymal Stem Cells: Enhance Hematopoiesis after Cord Blood Transplantation. Cell Transplant. 2013 Feb 26. Doi: 10.3727/096368913ZX663523 PubMed PMID: 23452720 (http://www.ncbi.nlm.nih.gov/pubmed/23452720)

6. Wu Y et al. Cotransplantation of haploidentical hematopoietic and umbilical cord mesenchymal stem cells for severe aplastic anaemia: Successful engraftment and mild GVHD. Stem Cell Research. 2014 Jan 12(1):132-138. (http://dx.doi.org/10.1016/j.scr.2013.10.001)

7. Amorin b et al. mesenchymal stem cell therapy and acute graft vs host disease: a review. Hum Cell. 2014; 27(4): 137-150 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186969/)

8. Wu KH. Effective Treatment of Severe Steroid Resistant Acute graft vs Host Disease with Umbilical Cord-Derived Mesenchymal Stem cells. Transplantation. 2011 Jun 91(12):1412-1416 doi: 10.1097/TP.0b013e31821aba18

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