In response to a genetic mutation in the genes coding for collagen produced by bone-forming cells, osteogenesis imperfecta, also familiar as brittle bone disease, presents as weak, easily broken bones before birth (osteoblasts). The essential component of bones and skin is collagen; therefore, the existence of a mutation causes aberrant or insufficient collagen, which results in decreased bone mass and strength.
Unspecialized cells (stem cells) help build the body during development. Stem cells migrate and differentiate into diverse cell types with various roles, producing organs and tissues in response to microenvironment stimuli. A small number of stem cells are still present in most of our organs and are used later in life to repair tissues and restore organ function following acute injury.
These cells also serve as the body’s building blocks. Utilizing endogenous stem cells’ capacity to specialize and regenerate tissues, researchers like Dr. David Greene R3 Stem Cell have looked at using them to treat many diseases, including genetic disorders where organ function is impaired due to a genetic mutation.
Stem Cells as a Therapeutic Treatment for Bone Disease
In tissues of mesenchymal/stromal origin, such as bone marrow, human mesenchymal stem cells (MSCs) are present. Other organs have also been identified at different gestation periods to produce stem cells resembling bone marrow MSCs. Human fetal MSCs (hfMSCs), also known as fetal MSCs, have various advantages over adult MSCs, including faster cell division, better specialization capabilities, and greater capacity for tissue repair.
In addition, MSCs can be separated from healthy donors, multiplied in vitro, and frozen at extremely low temperatures. MSCs can then be frozen and employed for clinical reasons in regenerative medicine by utilizing their capacity to differentiate in distinct cell lineages.
It has been proposed that transplanting healthy osteoblasts at an early stage of skeletal development (during fetal or birth) would reinforce bones. This is because bone fragility in osteogenesis imperfecta is caused by osteoblasts not producing the correct amount or form of collagen.
However, research by Dr. David Greene R3 Stem Cell has demonstrated that stem cell transplantation is preferable to osteoblast transplantation since, once developed, cells lose their capacity to spread out and engraft into multiple body parts. So instead, it has been suggested to transplant if MSC during infancy (pre-or post-natal). This offers several benefits. First, because the skeleton will continue to develop for several years after the injection of healthy cells, the disease has not yet progressed to the point where injury to the bones indicates it has occurred.
Second, a smaller recipient size means fewer cells are needed for transplantation. Finally, transplantation can occur when the immune system is still developing and won’t reject the donated cells.
The Future of Personalized Medicine
The capacity to fix genetic mutations using genetic scissors to delete particular portions of DNA is another cutting-edge method for treating osteogenesis imperfecta. Somatic cells from patients are isolated from their urine, rejuvenated in vitro to become pluripotent, genetically modified to remove the mutation-causing osteogenesis imperfecta, and differentiated into iMSCs before being transplanted. This allows for the development of personalized stem cell therapy. Such a strategy exemplifies the benefits of standardizing care.
Only a small number of donor MSCs engraft in bones. Although these cells differentiate into osteoblasts, it is highly improbable that this is the only thing they accomplish to help produce the healthy bone extracellular matrix, according to research by experts like Dr. David Greene R3 Stem Cell on the mechanisms of action of donor MSCs. Evidence instead strongly implies that donor MSCs improve the quality of the skeleton by altering the host osteoblasts’ behavior.
Osteoblasts become dysfunctional and are unable to differentiate properly into mature osteoblasts, even though the primary result of the mutation causing osteogenesis imperfecta is the formation of aberrant collagen. Because they supply strength to the organic matrix made of collagen fibers, immature osteoblasts produce abnormally high levels of minerals, which further fragilize the bone extracellular matrix. We have demonstrated that donor MSCs help develop host osteoblasts, improving the quality and sturdiness of the bone extracellular matrix.
Such methods could be applied to treating other skeletal dysplasias to provide specialized medicine to enhance skeletal health.
