Manufacturing of human placenta‐derived mesenchymal stem cells for clinical trials

Abstract

SummaryMesenchymal stem cells (MSC) are being used increasingly in clinical trials for a range of regenerative and inflammatory diseases. Bone marrow is the traditional source but is relatively inaccessible in large volume. MSC have now been derived from tissues other than bone marrow including placenta and adipose tissue. We have used placenta obtained after delivery as a source of MSC and have been unable to detect any marked differences from marrow-derived MSC in terms of cell surface phenotype, chemokine receptor display, mesodermal differentiation capacity or immunosuppressive ability. This report described our manufacturing process for isolating and expanding placenta-derived human MSC and their safe infusion into the first patient in a clinical trial program of human placenta-derived MSC.

Isolation and Expansion of Mesenchymal Stem/Stromal Cells Derived from Human Placenta Tissue

“…MSC cell surface marker profiles may be different depending on MSC tissue source, medium composition, or passage number 22 . In our many years of experience, we have not observed long-term contamination of placental-derived MSC with non-mesenchymal cells following 1-2 passages 5,11 . Placental MSC display mesenchymal differentiation potential By definition, MSC must possess in vitro mesodermal differentiation capacity 5,13 .…”

Exploring the Human Term Placenta as a Novel Source for Stem Cells and their Application in the Clinic

“…Importantly, we also showed that the immune suppressive capacity of hpMSC to decrease T cell alloreactivity in mixed lymphocyte reaction (MLR) was equivalent to that of hbmMSC . This thus suggested that human placenta is a potentially viable alternative source for human MSC and with this knowledge we are currently investigating placental-derived MSC in several human clinical trials (Brooke et al, 2009).…”

“…For these reasons, novel sources of MSC are now being investigated for clinical use in diseases in which the regenerative and immunomodulatory functions of MSC may be useful (Barlow et al, 2008b, Chang et al, 2006a, Brooke et al, 2009. A readily available and younger source that can be obtained by a non-invasive procedure, and which yields large numbers of MSC for ex vivo expansion would be an ideal alternative to adult bone marrow.…”

Multipotent mesenchymal stem cells from human placenta: critical parameters for isolation and maintenance of stemness after isolation

“…10 Mechanical as well as enzymatic methods for MSC isolation from different regions of human placenta of different gestational ages were reported (Table 1, see references therein). 5,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Knowledge about vitality, karyotype, phenotype and expandability of such placenta-derived MSC isolates is a prerequisite for therapeutic application, however systematic investigations into reliability of this MSC source and phenotypic stability have not yet been attempted. Further, former reports on placenta-derived MSCs often lack information about the karyotype of the cell isolates.…”