16 May 2014

Induced stem cells can replace bone defects

In experiments on an animal model closest to humans, the researchers demonstrated the possibility of forming new bone tissue from induced pluripotent stem cells (iPSCs) derived from the animals' own cells. The results of the study also indicate that iPSCs can give rise to tumors, but the probability of this is very low.

Researchers of the National Institute of Heart, Lung and Blood Diseases of the USA, working under the leadership of Cynthia Dunbar, used rhesus monkeys, whose physiology is very close to human physiology, as an animal model to study the possibility of therapeutic use of autologous iPSCs.

First, they applied a standard reprogramming protocol to skin fibroblasts, bone marrow stem cells and hematopoietic stem (CD34+) cells of monkeys. The resulting induced pluripotent stem cells were cultured under conditions that ensured their differentiation into mesenchymal stem cells capable of giving rise to connective tissue cells, including osteocytes (bone tissue cells).

The resulting cells were mixed with ceramic particles, currently used by plastic surgeons to fill in bone defects, and injected under the skin of monkeys. As a control, autologous bone marrow stem cells and cell-free ceramic material were implanted into the animals.

As a result, after 8 weeks in the areas of stem cell implantation, regardless of their origin, the formation of bone tissue was recorded, the histological characteristics of which in all cases corresponded to the parameters of bone tissue formed by bone marrow stem cells. Tissue formation was not observed in the implantation zones of ceramic particles.

The researchers also note that an important point is the absence of teratomas in the implantation zones – tumors formed by embryonic and undifferentiated induced pluripotent stem cells and consisting of cells of various types. A second check carried out 27-39 weeks after implantation confirmed the presence of stable bone structures and the absence of teratomas.

Numerous experiments, in which different doses of autologous mesenchymal stem cells obtained from iPSC in combination with various natural and artificial materials were injected under the skin of animals, demonstrated that these cells are able to form teratomas under the conditions of the body, but this happens only under favorable conditions: with a high concentration of cells and compounds that stimulate the growth of teratomas, such as extracellular matrix proteins.

The authors believe that the approach developed by them can form the basis for methods of regeneration of significant congenital or bone tissue defects that do not require constant immunosuppressive therapy. Currently, they, together with other research groups, are working on methods for differentiating iPSCs of macaques into liver cells, heart cells and leukocytes. The ultimate goal of this work is to conduct clinical trials involving patients with hepatitis C, heart failure and chronic granulomatosis.

Article by So Gun Hong et al. Path to the Clinic: Assessment of iPSC-Based Cell Therapies In Vivo in a Nonhuman Primate Model is published in the journal Cell Reports.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of ScienceDaily:
First test of pluripotent stem cell therapy in monkeys is successful.

16.005.2014

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