2016Regenerative TherapyOpen access

Comparison of capacities to maintain hematopoietic stem cells among different types of stem cells derived from the placenta and umbilical cord

Eri Nishikawa, Tarô Matsumoto, Mika Isige, Takashi Tsuji, H Mugisima, Syouri Takahashi

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Abstract

INTRODUCTION: Cord blood is utilized as a useful source of cells for hematopoietic stem cell transplantation, but this can be problematic because there is a high rate of graft failure compared to when other graft sources are used. A previous study successfully avoided graft failure by simultaneously grafting cord blood and bone marrow mesenchymal stem cells (MSCs) that are considered to function in the hematopoietic stem cell niche of the bone marrow.Organs of the fetal life support system such as the placenta and umbilical cord, which are discarded after delivery, contain an abundance of MSCs as well as cells that function in the hematopoietic stem cell niche. By identifying and collecting such cells and subsequently co-transplanting them with cord blood, an improvement in graft survival can be anticipated. METHODS: Three types of stem cells, amnion epithelial stem cells (AM-Epi), amnion mesenchymal stem cells (AM-Mes), and Wharton's jelly (WJ)-MSCs, all of which can be isolated and cultured from the placenta amnion or umbilical cord WJ, were investigated for the expression of hematopoietic stem cell niche markers and for their capabilities to maintain hematopoietic stem cells when co-cultured with cord blood hematopoietic stem cells. RESULTS: All types of isolated cells showed profiles that met the MSC minimal criteria according to surface marker analysis. In addition, all cell types expressed the hematopoietic stem cell niche marker stromal cell-derived factor-1 (SDF-1) (in order: AM-Epi > WJ-MSCs ≫ AM-Mes), although the expression declined with further passaging.After 5 days of co-culturing with cord blood CD34+ cells, the percentages of CD34+, CD45- cells were: AM-Epi 37.8%, AM-Mes 38.8%, WJ-MSCs 27.3%, and fibroblasts 27.4%; and the number of CFU-GM colonies were: AM-Epi 255.5 ± 21.6, AM-Mes 246.3 ± 28.5, WJ-MSCs 118.3 ± 11.8, fibroblasts 147.8 ± 19.0, and NC 121.3 ± 6.5. Statistical analyses demonstrated that AM-Epi and AM-Mes produced significantly greater numbers of CFU-GM compared to WJ-MSC, fibroblasts, or NC (p < 0.05). CONCLUSIONS: These findings indicated that cells derived from the fetal life support system such as AM-Epi and AM-Mes can be anticipated as potential cell sources for clinical application in cell therapies for the purpose of enhancing graft survival during hematopoietic stem cell transplantation.

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INTRODUCTION: Cord blood is utilized as a useful source of cells for hematopoietic stem cell transplantation, but this can be problematic because there is a high rate of graft failure compared to when other graft sources are used. A previous study successfully avoided graft failure by simultaneously grafting cord blood and bone marrow mesenchymal stem cells (MSCs) that are considered to function in the hematopoietic stem cell niche of the bone marrow.Organs of the fetal life support system such as the placenta and umbilical cord, which are discarded after delivery, contain an abundance of MSCs as well as cells that function in the hematopoietic stem cell niche. By identifying and collecting such cells and subsequently co-transplanting them with cord blood, an improvement in graft survival can be anticipated. METHODS: Three types of stem cells, amnion epithelial stem cells (AM-Epi), amnion mesenchymal stem cells (AM-Mes), and Wharton's jelly (WJ)-MSCs, all of which can be isolated and cultured from the placenta amnion or umbilical cord WJ, were investigated for the expression of hematopoietic stem cell niche markers and for their capabilities to maintain hematopoietic stem cells when co-cultured with cord blood hematopoietic stem cells. RESULTS: All types of isolated cells showed profiles that met the MSC minimal criteria according to surface marker analysis. In addition, all cell types expressed the hematopoietic stem cell niche marker stromal cell-derived factor-1 (SDF-1) (in order: AM-Epi > WJ-MSCs ≫ AM-Mes), although the expression declined with further passaging.After 5 days of co-culturing with cord blood CD34+ cells, the percentages of CD34+, CD45- cells were: AM-Epi 37.8%, AM-Mes 38.8%, WJ-MSCs 27.3%, and fibroblasts 27.4%; and the number of CFU-GM colonies were: AM-Epi 255.5 ± 21.6, AM-Mes 246.3 ± 28.5, WJ-MSCs 118.3 ± 11.8, fibroblasts 147.8 ± 19.0, and NC 121.3 ± 6.5. Statistical analyses demonstrated that AM-Epi and AM-Mes produced significantly greater numbers of CFU-GM compared to WJ-MSC, fibroblasts, or NC (p < 0.05). CONCLUSIONS: These findings indicated that cells derived from the fetal life support system such as AM-Epi and AM-Mes can be anticipated as potential cell sources for clinical application in cell therapies for the purpose of enhancing graft survival during hematopoietic stem cell transplantation.

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Available abstract

INTRODUCTION: Cord blood is utilized as a useful source of cells for hematopoietic stem cell transplantation, but this can be problematic because there is a high rate of graft failure compared to when other graft sources are used. A previous study successfully avoided graft failure by simultaneously grafting cord blood and bone marrow mesenchymal stem cells (MSCs) that are considered to function in the hematopoietic stem cell niche of the bone marrow.Organs of the fetal life support system such as the placenta and umbilical cord, which are discarded after delivery, contain an abundance of MSCs as well as cells that function in the hematopoietic stem cell niche. By identifying and collecting such cells and subsequently co-transplanting them with cord blood, an improvement in graft survival can be anticipated. METHODS: Three types of stem cells, amnion epithelial stem cells (AM-Epi), amnion mesenchymal stem cells (AM-Mes), and Wharton's jelly (WJ)-MSCs, all of which can be isolated and cultured from the placenta amnion or umbilical cord WJ, were investigated for the expression of hematopoietic stem cell niche markers and for their capabilities to maintain hematopoietic stem cells when co-cultured with cord blood hematopoietic stem cells. RESULTS: All types of isolated cells showed profiles that met the MSC minimal criteria according to surface marker analysis. In addition, all cell types expressed the hematopoietic stem cell niche marker stromal cell-derived factor-1 (SDF-1) (in order: AM-Epi > WJ-MSCs ≫ AM-Mes), although the expression declined with further passaging.After 5 days of co-culturing with cord blood CD34+ cells, the percentages of CD34+, CD45- cells were: AM-Epi 37.8%, AM-Mes 38.8%, WJ-MSCs 27.3%, and fibroblasts 27.4%; and the number of CFU-GM colonies were: AM-Epi 255.5 ± 21.6, AM-Mes 246.3 ± 28.5, WJ-MSCs 118.3 ± 11.8, fibroblasts 147.8 ± 19.0, and NC 121.3 ± 6.5. Statistical analyses demonstrated that AM-Epi and AM-Mes produced significantly greater numbers of CFU-GM compared to WJ-MSC, fibroblasts, or NC (p < 0.05). CONCLUSIONS: These findings indicated that cells derived from the fetal life support system such as AM-Epi and AM-Mes can be anticipated as potential cell sources for clinical application in cell therapies for the purpose of enhancing graft survival during hematopoietic stem cell transplantation.

Key concepts: Stem cell, Cord blood, Haematopoiesis, Adult stem cell, Umbilical cord, Mesenchymal stem cell, Cord lining, Amniotic stem cells

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