Much of the work conducted on adult stem cells has focused on mesenchymal stem cells (MSCs) found within the bone marrow stroma. Adipose tissue, like bone marrow, is derived from the embryonic mesenchyme and contains a stroma that is easily isolated. Preliminary studies have recently identified a putative stem cell population within the adipose stromal compartment. This cell population, termed processed lipoaspirate (PLA) cells, can be isolated from human lipoaspirates and, like MSCs, differentiate toward the osteogenic, adipogenic, myogenic, and chondrogenic lineages. To confirm whether adipose tissue contains stem cells, the PLA population and multiple clonal isolates were analyzed using several molecular and biochemical approaches. PLA cells expressed multiple CD marker antigens similar to those observed on MSCs. Mesodermal lineage induction of PLA cells and clones resulted in the expression of multiple lineage-specific genes and proteins. Furthermore, biochemical analysis also confirmed lineage-specific activity. In addition to mesodermal capacity, PLA cells and clones differentiated into putative neurogenic cells, exhibiting a neuronal-like morphology and expressing several proteins consistent with the neuronal phenotype. Finally, PLA cells exhibited unique characteristics distinct from those seen in MSCs, including differences in CD marker profile and gene expression.

/pdf/human-adipose-tissue-is-a-source-of-multipotent-stem-cells-18jo72s52v.pdf

Human Adipose Tissue Is a Source of Multipotent Stem Cells

Mesenchymal stem cells: clinical applications and biological characterization

Objective
To compare the properties of human mesenchymal stem cells (MSCs) isolated from bone marrow, synovium, periosteum, skeletal muscle, and adipose tissue.

Methods
Human mesenchymal tissues were obtained from 8 donors during knee surgery for ligament injury. After collagenase digestion or gradient-density separation, nucleated cells were plated at an appropriate density for expansion at the maximum rate without colony-to-colony contact. Yield, expandability, differentiation potential, and epitope profile were compared among MSCs from the 5 different tissue sources.

Results
Colony number per 103 nucleated cells was lower, and cell number per colony was higher, in bone marrow than in other mesenchymal tissues. When the cells were replated at low density every 14 days, bone marrow–, synovium-, and periosteum-derived cells retained their proliferation ability even at passage 10. In chondrogenesis studies in which the cells were pelleted and cultured in vitro, pellets from bone marrow–, synovium-, and periosteum-derived cells were shown to be larger and stained more extensively for cartilage matrix. Synovium-derived cells, in particular, had the greatest ability for chondrogenesis. In adipogenesis experiments, the frequency of oil red O–positive colonies was highest in synovium- and adipose tissue–derived cells. In studies of osteogenesis, the rate of alizarin red–positive colonies was highest in bone marrow–, synovium-, and periosteum-derived cells. For epitope profiling, 15 surface antigens were measured. Most appeared to have similar epitope profiles irrespective of cell source.

Conclusion
Our findings indicate that there are significant differences in MSC properties according to tissue source, beyond donor and experimental variation. Superiority of synovium as a potential source of MSCs for clinical applications was demonstrated.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.21212

Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source

Background: There is evidence that stern cells contribute to the restoration of tissue vascularisation and organ function. The objective of this study was to assess the presence of adipose derived adult stern cells left in their natural scaffold in the purified lipoaspirate and to access the clinical effectiveness of lipoaspirate transplantation in the treatment of radiation side effects. Methods: This study was designed beginning with surgical procedures in 2002 and envisaging a continious patient follow up to 31 months. Twenty consecutive patients undergoing therapy for side effects of radiation treatment wiht severe symptoms or irreversible functiomn damage (LENT-SOMAscale grade 3 and 4) were enrolled. Purified autologous lipoaspirates (60 to 120 cc) taken from a healthy donor site were administered by reperted low-invasive computer-assisted injection. Therapy outcomes were assessed by symptoms classification according to the LENT-SOMA scale, cytofluorrimetric characterization, and ultrastructural evaluation of targeetd tissue. Results: In the isolated stromal vascular fraction of 2 cc of human lipoaspirate, cells with mesenchymal stren cell physical proprieties and immunophenotype were in average 1.07 ± 0.5 percent (n=4), with a clonogenic fraction of 0.139 percent. At least 1.02 × 10 3 colony-forming units-fibroblast were present in cach lipoaspirate. Ultrastructure of target tissue systematically exhibited progressive regeneration, including neovessel formation and improved hydratation. Clinical outcomes led to a systematic improvement or remission of symptoms in all evaluated patients, including otherwise untreatable patients exhibiting initial irreversible functional damage. Conclusions: This surgical procedure is a low invasive therapeutic approach for resolving the late side effects of radiotherapy. According to the proposed hypothesis of the ischernic nature of radiolesions treatment with lipoaspirate transplantation is potentially extended to other forms of microangiopathies.

/pdf/clinical-treatment-of-radiotherapy-tissue-damage-by-4pp8dasvis.pdf

Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adipose-derived adult stem cells.

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.

Our laboratory has recently characterized a population of cells from adipose tissue, termed processed lipoaspirate (PLA) cells, which have multi-lineage potential similar to bone-marrow-derived mesenchymal stem cells (MSCs). This study is the first comparison of PLA cells and MSCs isolated from the same patient. No significant differences were observed for yield of adherent stromal cells, growth kinetics, cell senescence, multi-lineage differentiation capacity, and gene transduction efficiency. Adipose tissue is an abundant and easily procured source of PLA cells, which have a potential like MSCs for use in tissue-engineering applications and as gene delivery vehicles.

Bert Thomas

Papers

Comparison of Multi-Lineage Cells from Human Adipose Tissue and Bone Marrow