Mesenchymal stem cells (MSCs) represent a promising tool for new clinical concepts in supporting cellular therapy. Bone marrow (BM) was the first source reported to contain MSCs. However, for clinical use, BM may be detrimental due to the highly invasive donation procedure and the decline in MSC number and differentiation potential with increasing age. More recently, umbilical cord blood (UCB), attainable by a less invasive method, was introduced as an alternative source for MSCs. Another promising source is adipose tissue (AT). We compared MSCs derived from these sources regarding morphology, the success rate of isolating MSCs, colony frequency, expansion potential, multiple differentiation capacity, and immune phenotype. No significant differences concerning the morphology and immune phenotype of the MSCs derived from these sources were obvious. Differences could be observed concerning the success rate of isolating MSCs, which was 100% for BM and AT, but only 63% for UCB. The colony frequency was lowest in UCB, whereas it was highest in AT. However, UCB-MSCs could be cultured longest and showed the highest proliferation capacity, whereas BM-MSCs possessed the shortest culture period and the lowest proliferation capacity. Most strikingly, UCB-MSCs showed no adipogenic differentiation capacity, in contrast to BM- and AT-MSCs. Both UCB and AT are attractive alternatives to BM in isolating MSC: AT as it contains MSCs at the highest frequency and UCB as it seems to be expandable to higher numbers.

Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue.

The emerging field of regenerative medicine will require a reliable source of stem cells in addition to biomaterial scaffolds and cytokine growth factors. Adipose tissue represents an abundant and accessible source of adult stem cells with the ability to differentiate along multiple lineage pathways. The isolation, characterization, and preclinical and clinical application of adipose-derived stem cells (ASCs) are reviewed in this article.

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Adipose-Derived Stem Cells for Regenerative Medicine

Adipose tissue represents an abundant and accessible source of multipotent adult stem cells and is used by many investigators for tissue engineering applications; however, not all laboratories use cells at equivalent stages of isolation and passage. We have compared the immunophenotype of freshly isolated human adipose tissue-derived stromal vascular fraction (SVF) cells relative to serial-passaged adipose-derived stem cells (ASCs). The initial SVF cells contained colony-forming unit fibroblasts at a frequency of 1:32. Colony-forming unit adipocytes and osteoblasts were present in the SVF cells at comparable frequencies (1:28 and 1:16, respectively). The immunophenotype of the adipose-derived cells based on flow cytometry changed progressively with adherence and passage. Stromal cell-associated markers (CD13, CD29, CD44, CD63, CD73, CD90, CD166) were initially low on SVF cells and increased significantly with successive passages. The stem cell-associated marker CD34 was at peak levels in the SVF cells and/or early-passage ASCs and remained present, although at reduced levels, throughout the culture period. Aldehyde dehydrogenase and the multidrug-resistance transport protein (ABCG2), both of which have been used to identify and characterize hematopoietic stem cells, are expressed by SVF cells and ASCs at detectable levels. Endothelial cell-associated markers (CD31, CD144 or VE-cadherin, vascular endothelial growth factor receptor 2, von Willebrand factor) were expressed on SVF cells and did not change significantly with serial passage. Thus, the adherence to plastic and subsequent expansion of human adipose-derived cells in fetal bovine serum-supplemented medium selects for a relatively homogeneous cell population, enriching for cells expressing a stromal immunophenotype, compared with the heterogeneity of the crude SVF.

https://stemcellsjournals.onlinelibrary.wiley.com/doi/pdf/10.1634/stemcells.2005-0234

Immunophenotype of human adipose-derived cells: temporal changes in stromal-associated and stem cell-associated markers.

Compared with bone marrow-derived mesenchymal stem cells, adipose tissue-derived stromal cells (ADSC) do have an equal potential to differentiate into cells and tissues of mesodermal origin, such as adipocytes, cartilage, bone, and skeletal muscle. However, the easy and repeatable access to subcutaneous adipose tissue and the simple isolation procedures provide a clear advantage. Since extensive reviews focusing exclusively on ADSC are rare, it is the aim of this review to describe the preparation and isolation procedures for ADSC, to summarize the molecular characterization of ADSC, to describe the differentiation capacity of ADSC, and to discuss the mechanisms and future role of ADSC in cell therapy and tissue engineering. An initial effort has also been made to differentiate ADSC into hepatocytes, endocrine pancreatic cells, neurons, cardiomyocytes, hepatocytes, and endothelial/vascular cells. Whereas the lineage-specific differentiation into cells of mesodermal origin is well understood on a molecular basis, the molecular key events and transcription factors that initially allocate the ADSC to a lineage-specific differentiation are almost completely unknown. Decoding these molecular mechanisms is a prerequisite for developing novel cell therapies.

https://stemcellsjournals.onlinelibrary.wiley.com/doi/epdf/10.1634/stemcells.2006-0589

Concise review: adipose tissue-derived stromal cells--basic and clinical implications for novel cell-based therapies.

https://www.cell.com/trends/biotechnology/pdf/S0167-7799(06)00028-X.pdf

Fat tissue: an underappreciated source of stem cells for biotechnology

Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo

Role of Wnt5a in the proliferation of human glioblastoma cells.

Human bone marrow stromal cells (hBMSCs) are defined as pluripotent progenitor cells with the ability to differentiate into osteoblasts, chondrochytes, adipocytes, muscle cells, and neural cells. Recently, it has been shown that telomerase expression not only extends the replicative life-span and maintains their bone-forming capability of hBMSCs. We previously reported that human adipose tissue stromal cells (hATSCs) have similar characteristics with hBMSCs. In this study, hATSCs were stably tranduced by a retrovirus containing the gene for the catalytic subunit of human telomerase (hTERT) and MSCV-neo retrovirus, and 12 clones for hTERT-hATSCs and 6 clones for MSCV-hATSCs were isolated. The tranduced clones (hATSC-TERTs) had high telomerase activity, which was maintained during subsequent subcultivation. The transduced cells of two representative clones have undergone more than 100 population doublings (PD) and continue to proliferate, whereas control cells underwent senescence-associated proliferation arrest after 36-40 PD. The cells had a normal karyotype, and increased differentiation potential, especially osteogenic lineage. Intraventricular injection of hATSC-TERTs in ischemic rat brain showed enhancement of functional recovery as like hATSC-MSCVs. The tissue engraftment of hATSCs and hTERT-hATSCs in NOD/SCID mice after intravenous administration was identical. These results further support a similarity between hBMSCs and hATSCs. hATSCs can be used as an alternative of pluripotent stromal cells for cell replacement therapy as like hBMSCs.

Su Young Suh

Papers

Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo

Role of Wnt5a in the proliferation of human glioblastoma cells.

Expression of telomerase extends longevity and enhances differentiation in human adipose tissue-derived stromal cells.