Efficient in vitro generation of adult multipotent cells from mobilized peripheral blood CD133+ cells

TY - JOUR

T1 - Efficient in vitro generation of adult multipotent cells from mobilized peripheral blood CD133+ cells

AU - Kuçi, S

AU - Kuçi, Z

AU - Schmid, S

AU - Seitz, G

AU - Müller, I

AU - Dufke, A

AU - Leimig, T

AU - Murti, G

AU - Jurecic, R

AU - Schumm, M

AU - Lang, P

AU - Bruchelt, G

AU - Bader, P

AU - Klingebiel, T

AU - Niethammer, D

AU - Handgretinger, R

PY - 2008/2

Y1 - 2008/2

N2 - OBJECTIVES: To generate non-haematopoietic tissues from mobilized haematopoietic CD133(+) stem cells.MATERIALS AND METHODS: Mobilized peripheral blood CD133(+) cells from adult healthy donors were used. In vitro ability of highly enriched CD133(+) cells from mobilized peripheral blood to generate multipotent cells, and their potential to give rise to cells with characteristics of neuroectoderm, endoderm and mesoderm layers was investigated.RESULTS: We found that a recently identified population of CD45(+) adherent cells generated in vitro after culture of highly purified CD133(+) cells for 3-5 weeks with Flt3/Flk2 ligand and interleukin-6 can, in presence of the appropriate microenvironmental cues, differentiate into neural progenitor-like cells (NPLCs), hepatocyte-like cells and skeletal muscle-like cells. We have termed them to be adult multipotent haematopoietic cells (AMHCs). AMHC-derived NPLCs expressed morphological, phenotypic and molecular markers associated with primary neural progenitor cells. They can differentiate into astrocyte-like cells, neuronal-like cells and oligodendrocyte-like cells. Moreover, AMHC-derived NPLCs produced 3,4-dihydrophenylalanine and dopamine and expressed voltage-activated ion channels, suggesting their functional maturation. In addition, AMHC-derived hepatocyte-like cells and skeletal muscle-like cells, showed typical morphological features and expressed primary tissue-associated proteins.CONCLUSION: Our data demonstrate that AMHCs may therefore serve as a novel source of adult multipotent cells for autologous replacement cell therapies.

AB - OBJECTIVES: To generate non-haematopoietic tissues from mobilized haematopoietic CD133(+) stem cells.MATERIALS AND METHODS: Mobilized peripheral blood CD133(+) cells from adult healthy donors were used. In vitro ability of highly enriched CD133(+) cells from mobilized peripheral blood to generate multipotent cells, and their potential to give rise to cells with characteristics of neuroectoderm, endoderm and mesoderm layers was investigated.RESULTS: We found that a recently identified population of CD45(+) adherent cells generated in vitro after culture of highly purified CD133(+) cells for 3-5 weeks with Flt3/Flk2 ligand and interleukin-6 can, in presence of the appropriate microenvironmental cues, differentiate into neural progenitor-like cells (NPLCs), hepatocyte-like cells and skeletal muscle-like cells. We have termed them to be adult multipotent haematopoietic cells (AMHCs). AMHC-derived NPLCs expressed morphological, phenotypic and molecular markers associated with primary neural progenitor cells. They can differentiate into astrocyte-like cells, neuronal-like cells and oligodendrocyte-like cells. Moreover, AMHC-derived NPLCs produced 3,4-dihydrophenylalanine and dopamine and expressed voltage-activated ion channels, suggesting their functional maturation. In addition, AMHC-derived hepatocyte-like cells and skeletal muscle-like cells, showed typical morphological features and expressed primary tissue-associated proteins.CONCLUSION: Our data demonstrate that AMHCs may therefore serve as a novel source of adult multipotent cells for autologous replacement cell therapies.

KW - Adult

KW - Antigens, CD

KW - Base Sequence

KW - Cell Differentiation

KW - Chromatography, High Pressure Liquid

KW - DNA Primers

KW - Dihydroxyphenylalanine

KW - Dopamine

KW - Glycoproteins

KW - Humans

KW - In Vitro Techniques

KW - Multipotent Stem Cells

KW - Patch-Clamp Techniques

KW - Peptides

KW - Reverse Transcriptase Polymerase Chain Reaction

U2 - 10.1111/j.1365-2184.2007.00502.x

DO - 10.1111/j.1365-2184.2007.00502.x

M3 - SCORING: Journal article

C2 - 18211283

VL - 41

SP - 12

EP - 27

JO - CELL PROLIFERAT

JF - CELL PROLIFERAT

SN - 0960-7722

IS - 1

ER -