Adipose tissue-derived mesenchymal stem cell | Beyond the Dish

Mesenchymal stem cells possess a cell-surface protein called ALK2. ALK2 acts as a receptor for bone-inducing growth factors. ALK2, for example, is expressed in cartilage and if mesenchymal stem cells express a constantly-active form of ALK2, known as caALK2, these cells are driven to become cartilage-making cells (known as chondrocytes).

Can this receptor be used to drive bone formation? It turns out that manipulating ALK2 can drive fat-based stem cells (ASCs) to become bone making cells that ultimately improve bone tissue engineering. Researchers from the laboratory of Benjamin Levi at Massachusetts General Hospital, Boston, Massachusetts have fiddled with ALK2 in mesenchymal stem cells to for formation of bone from ASCs, and to enhance bone regeneration in a living animal.

To do this, Levis team genetically manipulated mice so that they expressed a form of ALK2 that was constantly turned on known as caALK2. The fat-based MSCs were then isolated and analyzed for their ability to make bone in culture. caALK ASCs were much more responsive to bone-inducing growth factors. These cells also expressed a whole host of bone-specific genes (e.g., Alp, Runx2, Ocn, Ops) after seven days. Since the caALK2 MSCs did so well in culture, they were then tested in mice with skull defects. Bone formation was significantly higher in mice treated with caALK2-expressing ASCs than those treated with normal ASCs.

Thus, Levis laboratory has shown that by treating mice with fat-based stem cells that express a constitutively active ALK2 receptor showed significantly increased bone formation. This increased bone formation can also be harnessed to improve skull healing in mice with bone defects.

Dr. Chad Schmiedt, a veterinary surgeon from the University of Georgia (UGA) Veterinary Teaching Hospital, and his colleagues have used mesenchymal stem cells from the fat of cats to optimize the acceptance of a new kidney in cats.

The recipient of this kidney transplant was a four-year-old flame point Siamese male cat named Arthur. Arthurs owners brought him from Virginia to the University of Georgia after he was diagnosed with chronic renal failure about a year ago. Two other veterinary hospitals declined to operate on Arthur, since they did not deem this cat an optimal candidate for a kidney transplant. As it turns out, Arthur has trouble absorbing cyclosporine, which is the anti-rejection drug used to prevent the recipient of the kidney transplant from rejecting it.

Arthur

In his initial consultation with Arthurs owners, Schmiedt had the idea of using adult feline stem cells as a part of Arthurs immunosuppressive protocol. There was precedent for this, since a cat that was operated on at University of Georgia Veterinary Teaching Hospital in 2013 had received a kidney transplant with doses of its own mesenchymal stem cells to prevent rejection of the transplanted organ. This cat was doing well one year after surgery.

To the best of my knowledge, UGA is the only veterinary facility in the world to use adult stem cells in feline kidney transplantation, said Schmiedt, who actually heads UGAs feline kidney transplant program.

Schmiedt continued: We used feline adult stem cells in one other transplant that we did last year. A study published in 2012 found that the use of MSCs during renal transplant surgery i humans lowered the risk of acute organ rejection, decreased the risk of infection, and the patients had better estimated renal function one year after surgery.

Go here to see the original:
Adipose tissue-derived mesenchymal stem cell | Beyond the Dish