Stem Cells and Regenerative Medicine
Regenerative medicine is a therapeutic medical field that focuses on developing technologies that use stem cells to replace, engineer, or regenerate human or animal cells, tissues, or organs with the aim of restoring or establishing normal function. Stem cells have the capacity to self-renew and differentiate into different types of cells that are found in the body [1] [2].
I. Do Regenerative Medicine Use Embryonic Stem Cells?
To generate new cells, tissues and organs, this technology may rely on the use of embryonic stem cells (ES cells) that must be obtained from early developed embryos. However, this approach is highly controversial due to the ethical issues surrounding the use of embryos.
II. What are the Other Approaches to Obtain Stem Cells for Regenerative Medicine?
1- Induced pluripotent stem cells
To avoid ethical issues surrounding the use of embryos for the obtention of stem cells, researchers developed a different method that relies on cell reprogramming.
In this method, non-embryonic and mature cells (Somatic cells) are reprogrammed into stem cells using cloning methods that consist in promoting the expression of stem cells’ transcription factors such as OCT3/4, SOX2, KLF4, and C-Myc. These reprogrammed cells are called induced pluripotent stem cells (iPS).
2- Adult Tissue-Specific Stem cells
Adult stem cells or adult tissue-specific stem cells are non-embryonic stem cells found in the tissues and organs of adult individuals. They have the specific characteristics of self-renewal and generate differentiated and specialized cells that contribute to tissue homeostasis and regeneration following injuries or diseases. They are found in several organs including the brain, liver, bone marrow, eyes, gut, skin, and muscle.
3- Mesenchymal Stem Cells (MSCs)
Mesenchymal stem cells are multipotent stromal stem cells that can only differentiate into bone, cartilage, muscle, tendons, ligaments, and neurons. They are found in the bone marrow.
4- Umbilical Stem Cells
These stem cells are recovered from post-natal (after birth) umbilical cords that contain HSCs and MSCs found in the umbilical cord blood cells, umbilical cord vein, and amnion and placenta. Clinically, they are used to treat blood diseases such as leukemia.
5- Bone Marrow Stem Cells
The bone marrow is the niche of hematopoietic stem cells (HSCs) that generate cells of the blood which contribute to the transport of nutrients and oxygen, coagulation, and immunity. HSCs produce two types of progenitor cells: myeloid progenitors and lymphoid progenitors.
The myeloid progenitors generate erythrocytes (red blood cells), platelets for coagulation, and myeloblasts that produce basophil, eosinophil, neutrophil, and monocytes that contribute to immunity. Lymphoid progenitors produce lymphocytes T, and lymphocytes B are also key players in immunity.
Like umbilical stem cells that contain hematopoietic stem cells (HSCs), bone marrow stem cells are also clinically used to treat blood diseases such as leukemia.
III. What Are the Applications of Regenerative Medicine?
Several clinical trials are taking place to assess the feasibility of using stem cells for the treatment of diseases and conditions. These can be assessed through clinicaltrials.gov.
1- Neurology Applications
Stem cells are being clinically tested for the treatment of Parkinson’s disease using embryonic dopamine neurons, while MSCs, bone marrow cells, and HSCs are being tested for the treatment of paraplegia, spinal cord injury, and multiple sclerosis.
2- Respiratory Applications
MSCs derived from the umbilical cord and bone marrow are being investigated for the treatment of chronic lung disease and idiopathic pulmonary fibrosis.
3- Cardiology Applications
For the treatment of heart failure and ischemic cardiomyopathy, MSCs are being tested through intracardiac injections.
4- Rheumatology Applications
MSCs and HSCs are being investigated for the treatment of osteoarthritis and osteogenesis imperfecta by direct injection into the articulations or through perfusion.
5- Hematology Applications
Through perfusion alone or in combination with hematopoietic stem cell transplantation, MSCs are being tested for the treatment of Graft versus Host Disease (GvHD).
6- Gastroenterology Applications
Treatments of Liver disease and decompensated liver disease are being tested using intravenous injection or diffusion of MSCs, while HSCs are being investigated for the treatment of Crohn’s disease.
7- Orthopedics Applications
For the healing of fractures, osteoporosis, and joint resurfacing, bone grafts, MSCs and HSCs are being used.
8- Urology Applications
MSCs are being clinically tested for the prevention of kidney transplant rejection.
9- Endocrinology Applications
Stem cells from the cord blood are investigated for the treatment of insulin-resistant type II diabetes, while hematopoietic cell transplantation is used for diabetes type I.
10- Ophthalmology Applications
Endothelial stem cells from the retinal epithelium are used for the treatment of macular degeneration.
IV. Challenges of Regenerative Medicine.
Despite the significant advances in regenerative medicine, several challenging factors require further investigations to ensure its safe and ethical application for the treatment of diseases and conditions:
- The ethical use of embryonic stem cells is certainly an important factor in slowing down its application. Regenerative medicine is a subject of ethical, political, and religious controversies.
- Our body’s immune system that ensures our capacity to combat invading pathogens or cancer, may reject the stem cell therapy.
- The manufacturing of stem cell therapies is difficult to scale up and the associated cost is also significant.
- The stem cells that are used for stem cell therapies require screening to ensure that their genome is intact and does not contain mutations that could generate cancer upon transplantation into patients.
Conclusion
Regenerative medicine relies on the use of stem cells obtained from embryos, the umbilical cord, and adult stem cells that are found in some tissues of the adult body. However, regenerative medicine is also a multidisciplinary field that requires the contribution of other technologies such as stem cell and developmental biology, tissue engineering, nanotechnologies, chemical biology, and biomaterial engineering.
Although it is still considered an emerging therapeutic field, regenerative medicine is already showing an impact in the treatment of neurological, hematological, and rheumatological conditions. However, the progress of this field requires further clinical trials to ensure its safety and development in the clinic.
Solid data obtained through clinical trials with clear healthcare benefits will certainly promote public awareness about regenerative medicine which is already subject to ethical, political, and religious controversies.
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