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Stem Cells - Exploring Stem Cells and the Art of Organ Creation

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Organogenesis is the process of developing internal organs from embryonic stem cells. Read below to know more.

Written by

Dr. Asma. N

Medically reviewed by

Dr. Kaushal Bhavsar

Published At September 25, 2023
Reviewed AtFebruary 27, 2024

Introduction:

Organogenesis is the process where the internal organs are formed from the germ tissue layers of the embryo. These germ tissue or pluripotent stem cells are the primary cells, which can differentiate into many specific cells. These stem cells are useful in understanding the disease process, regenerative medicine, and testing new drugs in specific tissues. Recent technologies have developed in forming organoids with the help of pluripotent stem cells in specific media and with the help of growth factors.

What Is Organogenesis?

Organogenesis is the process of the formation of internal organs from the germ tissue layers of the embryo. These germ layers undergo a differentiation process to form internal organs. The embryonic stem cells express specific genes that determine the cell type. There are three types of germ tissue layers, which include:

  • Ectoderm: It is the outer layer of the three germ layers of the embryo. It develops into the nervous system and epidermis.

  • Mesoderm: It is the middle layer of the three germ layers of the embryo. It develops into the skeletal muscle, cardiac muscles, smooth muscle, red blood cells, and muscle tissues within the kidneys, spine, and circulatory system.

  • Endoderm: It is the innermost layer of the three germ layers of the embryo. It develops into the digestive system (except the pharynx and mouth), the last part of the rectum, lining cells of the pancreas and liver, the epithelium of the tympanic cavity and auditory tube, the urinary bladder, parts of the lungs, follicle lining of the thymus and thyroid gland, and internal organs such as colon, stomach, pancreas, liver, intestine, thyroid, and parathyroid.

What Are Stem Cells?

Stem cells are the primary cells from which other cells are differentiated. These stem cells can divide under proper conditions of the body or in the laboratory to form other cells called daughter cells. These daughter cells can differentiate into new stem cells and specialized cells such as brain, blood, bone, or heart muscle cells. Stem cells can be obtained from:

  • Embryonic Stem Cells: They are obtained from an embryo three to five days old, and the embryo stage is called a blastocyst; it has around 150 cells and can form any type of cell, therefore called pluripotent stem cells.

  • Adult Stem Cells: These are obtained from adult fat and bone marrow tissues. Bone marrow stem cells can form heart muscle cells and bone cells. Researchers have altered adult stem cells with the help of genetic reprogramming to produce cells similar to embryonic stem cells.

  • Perinatal Stem Cells: These stem cells are obtained from amniotic fluid (a fluid sac that covers the fetus) and umbilical cord blood.

Why Do Experts Find Stem Cells to Be So Interesting?

Experts believe that extensive studies on stem cells will help in the following:

  • Experts will better understand the development of certain diseases and syndromes by monitoring how the stem cells differentiate into various cells in bones, heart, lungs, and other organs.

  • Since stem cells can differentiate into various cells, they can be utilized to create new cells to replace the damaged cells in specific tissues or organs.

  • Spinal cord injuries, diabetes, Parkinson's disease, Alzheimer's disease, heart disease, stroke, burns, cancer, and osteoarthritis are conditions that could benefit from stem cell therapy.

  • Stem cells can be used in transplants because of their capability to grow into newer specified tissue.

  • Stem cells are utilized to test the efficacy of newly discovered drugs instead of testing on humans or animal models. However, it is important to consider that stem cells should possess the characteristics of a particular organ or tissue on which the drug will be effective before testing.

Why Is the Use of Embryonic Stem Cells Controversial?

Human embryonic stem cells are a kind of cells that can be extracted from a human embryo. These cells are formed when a sperm fertilizes an ovum. The National Institute of Health has established embryonic stem cell research regulations. Also, it included stem cells from embryos, which should be used only when the embryo is not required when developed through invitro fertilization in clinical settings.

What Is the Future of Stem Cells in Organogenesis by Tissue Engineering?

Organogenesis can help form transplantable organs with the help of embryonic tissues placed in the recipient's omentum (a layer connecting the stomach and other abdominal organs). This represents the future medicine of transplantation. This tissue engineering includes embryonic stem cells, adult stem cells, and germ cells. Embryonic stem cells have a high potential to differentiate into specific tissues. The selected cells are seeded in the dish and cultured in tissue engineering. Bioreactors help in the cells' growth until the organ's formation. Hence, this is a new era and requires more research and development. Some engineered tissues are:

  • Cerebral Brain Organoids and Optical Cups Derived From Ectoderm: Cerebral brain organoids are engineered from human induced pluripotent stem cells (hiPSCs), which are derived from neural progenitors in a bioreactor, and these show regional specifications like midbrain, hindbrain, and forebrain. If the cerebral organoids are derived from a patient with microcephaly, the formed neural tissues are small. In the presence of a Wnt inhibitor, the human embryonic stem cells (hPSCs), with the help of the modified SFEBq (serum-free, floating EB-like quick aggregates) culture, optical cups can be formed. This optical cup has outer retinal pigment epithelium and an inner layer of neurosensory cells.

  • Cardiac Microtissues Derived From Mesoderm: Cardiac cells, which are derived from hPSCs, can form cardiac bodies or cardiac tissues. However, these do not have complex organoid structures and require maturation with the help of 3-D scaffolds or by stimulating adult cell energy metabolism.

  • Intestine, Liver, and Islet Organoids Derived From Endoderm: These are derived with the help of WNT3A and FGF-4 treatment. Embedding these structures in matrigel can allow the cells to mature into intestinal organoids containing differentiated cell types. Embryonic stem cells can form thyroid follicular cells with the help of thyroid-stimulating hormones and overexpression of transcription factors like NKX2.1 and PAX8. Liver buds can be formed with the help of hiPSC-derived hepatocyte progenitors, human umbilical vein endothelial cells, and human mesenchymal stem cells. Growing organoids requires specific mechanisms and methods. Self-organization is a type of mechanism and includes programmed internal interactions and intrinsic tissue mechanics. It has three types: self-morphogenesis, self-assembly, and self-patterning. There should be an appropriate starting cell population for organoid formation. The pluripotent stem cells in which it is cultured should have growth factors such as Wnt inhibitors, epidermal growth factor, R-spondin-1, and noggin. 3D extracellular matrices such as collagen gel, matrigel, and fibrin gel are required to form functional organoids. Along with these, progenitor cells can be embedded. Bioreactors are used to increase the size of organoids.

Conclusion:

Tissue engineering with the help of pluripotent stem cells is a new phase in transplantation. Many tissue-specific cells have been grown in vitro with the help of stem cells in specific conditions. But this requires further development and research.

Dr. Kaushal Bhavsar
Dr. Kaushal Bhavsar

Pulmonology (Asthma Doctors)

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