Human Umbilical Cord Matrix Stem Cells: Preliminary Characterization and Effect of Transplantation in a Rodent Model of Parkinson's Disease

Abstract

The umbilical cord contains an inexhaustible, noncontroversial source of stem cells for therapy. In the U.S., stem cells found in the umbilical cord are routinely placed into biohazardous waste after birth. Here, stem cells derived from human umbilical cord Wharton's Jelly, called umbilical cord matrix stem (UCMS) cells, are characterized. UCMS cells have several properties that make them of interest as a source of cells for therapeutic use. For example, they 1) can be isolated in large numbers, 2) are negative for CD34 and CD45, 3) grow robustly and can be frozen/thawed, 4) can be clonally expanded, and 5) can easily be engineered to express exogenous proteins. UCMS cells have genetic and surface markers of mesenchymal stem cells (positive for CD10, CD13, CD29, CD44, and CD90 and negative for CD14, CD33, CD56, CD31, CD34, CD45, and HLA-DR) and appear to be stable in terms of their surface marker expression in early passage (passages 4 -8). Unlike traditional mesenchymal stem cells derived from adult bone marrow stromal cells, small populations of UCMS cells express endoglin (SH2, CD105) and CD49e at passage 8. UCMS cells express growth factors and angiogenic factors, suggesting that they may be used to treat neurodegenerative disease. To test the therapeutic value of UCMS cells, undifferentiated human UCMS cells were transplanted into the brains of hemiparkinsonian rats that were not immune-suppressed. UCMS cells ameliorated apomorphine-induced rotations in the pilot test. UCMS cells transplanted into normal rats did not produce brain tumors, rotational behavior, or a frank host immune rejection response. In summary, the umbilical cord matrix appears to be a rich, noncontroversial, and inexhaustible source of primitive mesenchymal stem cells. STEM CELLS 2006;24:781-792

Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: In vitro and in vivo analysis

“…Different harvesting procedures have led to UC-derived cells that exhibit a neuronal phenotype ( Fu et al, 2006;Mitchell et al, 2003;Sarugaser et al, 2005;Wang et al, 2004) and have potential utility in treatment of neurodegenerative diseases ( Weiss et al, , 2006, indicating the versatility of this cell source. Inter-estingly, these cells, which are major histocompatibility complex (MHC) class II negative, not only express immunoprivileged and immunomodulatory phenotype, but also their MHC class I expres-sion levels can be manipulated ( Sarugaser et al, 2005), making them a potential cell source for MSC-based therapies.…”

Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors

“…The methods to isolate and culture human UCMS cells were previously described. 3 MDA 231, a human breast carcinoma cell line that engrafts in the lung of nude mice 20 was maintained in Dulbecco's modified Eagle's medium (DMEM; Invitrogen, Carlsbad, CA), 1X Pen/Strep (Invitrogen, CA) and 10% fetal bovine serum (FBS) (Mediatech, Herndon, VA) at 371C in a humidified atmosphere containing 5% carbon dioxide.…”

“…The properties that promote their potential utility are the large number of cells recoverable from the umbilical cord, the noninvasive harvest following birth, and the abundant supply of umbilical cords. 2,3 Thus, they may offer an immediate avenue for cytotherapy, when time is of the essence for such therapy, for example, in cases of malignant neoplasia. UCMS cells transplanted into rodent neurodegenerative models [4][5][6] have been extensively characterized 3 and they express many of the genes expressed by primitive stem cells such as embryonic stem cells (ESCs).…”

“…2,3 Thus, they may offer an immediate avenue for cytotherapy, when time is of the essence for such therapy, for example, in cases of malignant neoplasia. UCMS cells transplanted into rodent neurodegenerative models [4][5][6] have been extensively characterized 3 and they express many of the genes expressed by primitive stem cells such as embryonic stem cells (ESCs). 7 They can be differentiated into a variety of cell types including muscle, 8 cartilage, 9 bone, 9 and neural 1 cells and have been used for tissue-engineered artificial blood vessels and heart valves.…”

Human umbilical cord-derived mesenchymal stem cells differentiate into epidermal-like cells using a novel co-culture technique

“…Greater numbers of MSCs have been isolated from the umbilical cord (termed hUCMSCs) as compared to umbilical cord blood (Secco et al 2008). hUCMSCs can be easily isolated from nearly all samples, even from those umbilical cords that have been stored for up to 48 h (Weiss et al 2006). Within Wharton's jelly, hUCMSCs have been isolated from three relatively indistinct regions, the perivascular zone, the intervascular zone, and the subamnion; however, whether hUCMSCs isolated from different compartments represent different populations has yet to be determined .…”