Future cell-based therapies such as tissue engineering will benefit from a source of autologous pluripotent stem cells. For mesodermal tissue engineering, one such source of cells is the bone marrow stroma. The bone marrow compartment contains several cell populations, including mesenchymal stem cells (MSCs) that are capable of differentiating into adipogenic, osteogenic, chondrogenic, and myogenic cells. However, autologous bone marrow procurement has potential limitations. An alternate source of autologous adult stem cells that is obtainable in large quantities, under local anesthesia, with minimal discomfort would be advantageous. In this study, we determined if a population of stem cells could be isolated from human adipose tissue. Human adipose tissue, obtained by suction-assisted lipectomy (i.e., liposuction), was processed to obtain a fibroblast-like population of cells or a processed lipoaspirate (PLA). These PLA cells can be maintained in vitro for extended periods with stable population doubling and low levels of senescence. Immunofluorescence and flow cytometry show that the majority of PLA cells are of mesodermal or mesenchymal origin with low levels of contaminating pericytes, endothelial cells, and smooth muscle cells. Finally, PLA cells differentiate in vitro into adipogenic, chondrogenic, myogenic, and osteogenic cells in the presence of lineage-specific induction factors. In conclusion, the data support the hypothesis that a human lipoaspirate contains multipotent cells and may represent an alternative stem cell source to bone marrow-derived MSCs.

/pdf/multilineage-cells-from-human-adipose-tissue-implications-4z32vwpf0q.pdf

Multilineage cells from human adipose tissue: implications for cell-based therapies.

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

Human mesenchymal stem cells modulate allogeneic immune cell responses

https://yunus.hacettepe.edu.tr/~damlacetin/kmu407/index_dosyalar/4.%20makale.pdf

Biodegradable polymers as biomaterials

Background Many risk factors for hip fractures have been suggested but have not been evaluated in a comprehensive prospective study. Methods We assessed potential risk factors, including bone mass, in 9516 white women 65 years of age or older who had had no previous hip fracture. We then followed these women at 4-month intervals for an average of 4.1 years to determine the frequency of hip fracture. All reports of hip fractures were validated by review of x-ray films. Results During the follow-up period, 192 women had first hip fractures not due to motor vehicle accidents. In multivariable age-adjusted analyses, a maternal history of hip fracture doubled the risk of hip fracture (relative risk, 2.0; 95 percent confidence interval, 1.4 to 2.9), and the increase in risk remained significant after adjustment for bone density. Women who had gained weight since the age of 25 had a lower risk. The risk was higher among women who had previous fractures of any type after the age of 50, were tall at the age of 25, rated their own health as fair or poor, had previous hyperthyroidism, had been treated with long-acting benzodiazepines or anticonvulsant drugs, ingested greater amounts of caffeine, or spent four hours a day or less on their feet. Examination findings associated with an increased risk included the inability to rise from a chair without using one's arms, poor depth perception, poor contrast sensitivity, and tachycardia at rest. Low calcaneal bone density was also an independent risk factor. The incidence of hip fracture ranged from 1.1 (95 percent confidence interval, 0.5 to 1.6) per 1,000 woman-years among women with no more than two risk factors and normal calcaneal bone density for their age to 27 (95 percent confidence interval, 20 to 34) per 1,000 woman-years among those with five or more risk factors and bone density in the lowest third for their age. Conclusions Women with multiple risk factors and low bone density have an especially high risk of hip fracture. Maintaining body weight, walking for exercise, avoiding long-acting benzodiazepines, minimizing caffeine intake, and treating impaired visual function are among the steps that may decrease the risk.

Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group.

Compression tests of human and bovine trabecular bone specimens with and without marrow in situ were conducted at strain rates of from 0.001 to 10.0 per second. A porous platen above the specimens allowed the escape of marrow during testing. The presence of marrow increased the strength, modulus, and energy absorption of specimens only at the highest strain rate of 10.0 per second. This enhancement of material properties at the highest strain rate was due primarily to the restricted viscous flow of marrow through the platen rather than the flow through the pores of the trabecular bone. In specimens without marrow, the strength was proportional to the square of the apparent density and the modulus was proportional to the cube of the apparent density. Both strength and modulus were approximately proportional to the strain rate raised to the 0.06 power. These power relationships, which were shown to hold for all bone in the skeleton, allow meaningful predictions of bone tissue strength and stiffness based on in vivo density measurements.

The compressive behavior of bone as a two-phase porous structure.

A mathematical analysis for indentation tests of articular cartilage.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/jor.1100160202

Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells.

We compared roentgenograms of the jumeri of a group of professional tennis players and showed that there was pronounced hypertrophy of bone on the playing side. The cortical thickness on that side was greater by 34.9 per cent in men and 28.4 per cent in women compared with the control side. This represents a highly significant hypertrophy of bone in response to exercise.

Humeral hypertrophy in response to exercise.

Controlled bending moments were applied to twelve human cadaver knee joints using a special loading fixture that allowed variation of both the Q-angle and the flexion angle. The joints were tested at three different Q-angles (physiological, increased 10 degrees, and decreased 10 degrees) and five different angles of flexion (ranging from 20 to 120 degrees). Based on one-third of values in the literature for maximum voluntary isometric quadriceps moments, we applied resultant knee moments of 23.6, 30.7, 47.2, and 35.0 newton-meters at 20, 30, 60, and 90 degrees of flexion, respectively. Based on two-thirds of reported maximum moments, we applied 47.2 newton-meters at 120 degrees of flexion. Normal patellofemoral-contact pressures, measured with a pressure-sensitive film, were remarkably uniformly distributed (+/- 0.25 megapascal ), with approximately the same pressure on the lateral and medial patellar facets. The maximum contact force occurred at 90 degrees of flexion. Extrapolating our measurements to full in vivo moments, we estimated maximum contact forces of 4600 newtons , or approximately 6.5 times body weight. Tendofemoral contact at 120 degrees of knee flexion supported one-third of the total contact force on the patella. A 10-degree increase in the Q-angle resulted in increased peak pressures (an increase of 45 per cent at 20 degrees of flexion). A decrease in the Q-angle resulted in unloading of the vertical crest and, in some knees, of parts of the lateral facet. However, these decreases were always associated with increased peak pressures (50 per cent more at 20 degrees of flexion) at other locations.

Wilson C. Hayes

Papers

The compressive behavior of bone as a two-phase porous structure.

A mathematical analysis for indentation tests of articular cartilage.

Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells.

Humeral hypertrophy in response to exercise.

Patellofemoral contact pressures. The influence of q-angle and tendofemoral contact.