INTRODUCTION:

Stem cells are undeveloped cells, grew to become specialised cells. Due to their differentiation capacity, they can differentiate into the cells of any organ in the body. They can also proliferate to produce fresh stem cells. Although stem cells are produced in the bone marrow, they are also found in our blood because the bone marrow releases them into the circulatory system. We may be able to govern stem cells in vitro if we can identify the genomic and proteomic regulators of stem cell proliferation.¹ Although stem cell technology is only now becoming available, the potential of a living thing to regenerate bodily parts has been known since 330 BC, when Aristotle noticed that a lizard could re-grow the tip of its missing tail. Since then, efforts have been made slowly but steadily to grasp the human body's capacity for regeneration, and it has only been in the past ten years that the amount of material available on stem cell research has exploded. The entire delivery of healthcare may undergo a change because of stem cells.²

In cellular treatment, stem cells can be employed to rebuild organs or to replace damaged cells. Furthermore, stem cells have improved our knowledge of both disease causation and development. It is also possible to grow and employ disease-specific cell lines for medication development. Many of the genes involved in controlling development in various species are now well known, and we have discovered inside of genetic pathway conservation across evolution.³

Numerous preclinical and small clinical studies conducted over the years have demonstrated that the injection of different types of stem cells, including adult stem cells, embryonic stem cells, stem cells derived from cord blood, and stem cells derived from bone marrow, into damaged or degenerating tissue, can induce tissue regeneration. Various levels of functional improvement have been observed in a number of modest clinical trials. ⁴ In this study we discuss the origin and varieties of stem cells, their utility in treating various diseases, and the dissemination of enlightening information in the future. This class of human stem cell holds the promise of being to repair or replace cells or tissues that are damaged or destroyed by many of our most devastating diseases and disabilities.²

With their unique ability to self-renew and give rise to specific cell types, stem cells are a rare and adaptable sort of cells that can divide endlessly. While the majority of body cells, such skin or heart cells, are dedicated to carrying out a specific task, stem cells are not committed and stay that way until they get a signal to differentiate into a specialized cell type. What sets stem cells apart is not just their capability for proliferation but also their propensity to become specialized.

Researchers were able to separate this type of pluripotent stem cell from early human embryos and cultivate them in culture for the first time in 1998. Since this discovery a few years ago, evidence has surfaced suggesting that these stem cells can differentiate into nearly every specialized cell in the body. As a result, they may be able to produce replacement cells for a wide range of tissues and organs, including the nervous system, the heart, and the pancreas. Therefore, many of our most debilitating illnesses and impairments have the potential to harm or destroy cells or tissues, and this class of human stem cells holds the hope of being able to replace or repair them.⁴

SOURCES OF STEM CELLS:

There are several sources of stem cells. Pluripotent stem cells can be extracted from human embryos at a few days old. Cells from these embryos can be used to create pluripotent stem cell "lines" cell cultures that can be cultured in the lab indefinitely. The two primary types of stem cells seen in humans are adult stem cells and embryonic stem cells.⁵ Bone marrow is the spongy substance that lies inside the bones and contains stem cells.

The three types of blood cells that the body requires are formed from stem cells: red blood cells, which transport oxygen throughout the body; White blood cells are immune system fighters. Platelets support the blood clot (PLATE-lets). Trace quantities of stem cells can be found in blood and the umbilical cord, which connects fetes to its mother's placenta. Autologous bone marrow transplantation, for instance, entails taking bone marrow out of a patient's bone and returning it to them in order to replenish hematopoietic stem cells. This is commonly used in leukemia patients. Stem cells from blood are easier to collect for research purposes.⁵

CORD BLOOD CELLS:

Autologous cord blood cells can be extracted, stored, and then safely reinjected into the baby without having to worry about the child developing an immune response against them. Cord blood stem cells are already being used to treat diseases including type 1 diabetes and brain injuries.

ADIPOSE TISSUE:

Adipose tissue contains a large number of adult stem cells. These stem cells possess multipotency, meaning they can differentiate into multiple cell types such as bone, muscle, cartilage, and nerve cells.

SKIN STEM CELLS:

Your skin's ongoing renewal (regeneration) and wound healing are controlled by skin stem cells. Thus far, researchers have discovered a wide variety of skin stem cells, such as:

· Epidermal stem cells are regularly renewed by the various layers of the epidermis. These stem cells are found in the basal layer of the epidermis.

· Hair follicles are continuously regenerating into hair follicle stem cells. The sebaceous and epidermal glands can regenerate from damage to these tissues. Hair follicle stem cells are present in every hair follicle, and melanocyte stem cells are responsible for the regeneration of melanocytes, a subset of pigment cells. Because melanocytes produce the pigment melanin, they have a major role in the colouring of skin and hair follicles.⁵

CLASSIFICATION BASED ON SOURCES OF STEM CELLS:

1. Embryonic Stem Cells: The inner cell mass of the blastocyst is harvested to obtain embryonic stem cells, which are produced seven to ten days after fertilization.

2. Fetalis Stem Cells: The germline parts of aborted foetuses from which the gonads will develop are used to isolate fetalis stem cells.

3. Umbilical cord Stem Cells: The stem cells found in umbilical cord blood are similar to those found in bone marrow.

4. Placental Stem Cells: Compared to cord blood, placental stem cells can be extracted in amounts up to ten times higher.

5. Adult Stem Cells: A number of adult tissues can have stem cells isolated from them.

6. Amniotic fluid: Multipotent stem cells are also present in this fluid.

7. Cancer Stem Cells: A subset of cancer cells, cancer stem cells can disseminate the disease, proliferate, and differentiate into any of the several cell types found in a tumour.

8. Induced Pluripotent: Instead of developing into adult stem cells, induced pluripotent cells are adult cells (like epithelial cells) that have undergone a reprogramming process to acquire pluripotent properties

9. Lineage: To guarantee self-renewal, stem cells undergo two distinct types of cell division. It's a part of a division.⁶

STEM CELL THERAPY:

1. Stem Cell Therapy: Cell-based therapy: The idea behind cell-based therapy, also known as just cell therapy occasionally, is to replace, repair, or add healthy cells to sick or damaged ones. Researchers that work with stem cells have already created ways to obtain these cells, which can be used to treat or even totally eradicate a variety of incurable diseases since they can grow into new, healthy cells or tissues when implanted.⁷

Stem Cell Transplantation: The transplantation of stem cells is an amazing field of medicine. It has a strong reputation as a treatment for certain cancers and blood diseases since a few decades ago.

1. Hodgkin's and Non-Hodgkin's Lymphoma: It is the standard treatment for cases that have relapsed or are resistant to treatment, and in most of these cases, it is the only option for recovery.

2. Myeloma: Due to its remarkable survival rate, myeloma medication is frequently administered as part of early therapy even if it is not curative.

3. Leukaemia: In order to increase the chance that acute myeloid leukaemia will be cured, consolidation treatment is being administered.

· Allogenic Transplantation: Stem Cells Derived from Another Person's Body

· Thalassemia: A number of other hereditary illnesses, especially those brought on by anomalies in a single gene

· Plastic Anaemia

· Chronic Myeloid Leukaemia

· Acute Lymphocytic Leukaemia (ALL) relapsed;

· High Risk AML relapsed;

· As an option in several resistant or advanced haematological cancers, including follicular lymphoma, myeloma, and CLL. The process primarily accomplishes three goals:

1. Replacing a gene that is absent, as in Sickle Cell Disease, Thalassemia, and many other hereditary illnesses. In patients who are otherwise healthy, replacing the missing gene can cure some illnesses.

2. Allows for the administration of strong anticancer medications, which may cause bone marrow loss. Bone marrow can only repair slowly in the absence of stem cells, which raises the possibility of bleeding or infections. Infused stem cells enable early blood cell repair. It considerably lowers the risk of marrow suppression-induced low blood counts. That's why it's called "Supportive Therapy" rather than a cancer treatment on its own. Both autologous (self) and most allogeneic transplants fall under this category.

3. In allogeneic transplants, there is a "Graft versus Disease activity," or "Graft v Leukaemia effect," which is especially evident in chronic myeloid leukaemia.

TYPES OF TRANSPLANTS:

The stem cells can be extracted from the patient's body or from the body of another individual. The name of this extra person is Donor.

Autologous Transplant:

After conditioning therapy, the patient's stem cells are extracted from their bone marrow or through apheresis (the extraction of peripheral blood stem cells).

Allogeneic transplant:

The donor's HLA type and the patients are the same. Stem cells are extracted from bone marrow or retrieved by aphaeresis (peripheral blood stem cells) from an HLA-matched donor, usually a brother or sibling.

1) Diabetes (Type-1 and Type-2):

The most successful treatment for diabetes mellitus is stem cell therapy because mesenchymal stem cells can develop into pancreatic beta-islet cells through in vitro culture. Because diabetes is an autoimmune metabolic disease that causes the body to attack its own pancreatic cells as foreign cells, the treatment with autologous bone marrow derived mesenchymal stem cells (MSCs) provides immune-regulatory properties and stops the immune attack by secreting anti-inflammatory cytokines (IL-10, TGF-beta, and I 1).

· Stem cell therapy for diabetic patients shows good improvement because the concentration of bone marrow-derived stem cells (CD44+, CD31+, and CD34+) can rebuild beta islets cells.^7-10

2) Acute/Chronic Liver Disease:

A number of clinical trials have shown that stem cell therapy is beneficial for treating liver-related conditions like end-stage liver disease (ESLDs) and acute liver failure. The theory is that, in cases of liver sickness, stem cells can differentiate into hepatocyte cells upon transplantation, improving the results of all liver related tests. ^11-12

3) Muscular Dystrophy:

Mesenchymal stem cell (MSC) therapy mainly targets the inflammatory response in muscular dystrophy, despite the fact that there is currently no known cure for the condition. Mesenchymal stem cells are a better option for treating muscular dystrophy than other cell-based therapies that have been tried. ^13-14

4) Kidney diseases:

The number of people with chronic kidney disease (CKD) is rising globally, but there is currently no cure for the illness. Thus, after a fruitful experiment on animals, scientists are now hopeful about its potential for use with humans. In chronic kidney disease, the defective cells in the vascular, interstitial, glomerular, and tubular compartments attract inflammatory cells to the injured kidneys and release fibro genic cytokines. The early implantation of scar tissue probably provides a survival advantage by preventing dangerous germs from entering the lesion, even while it hinders later tissue or kidney cell regeneration.

Due to the fact that mesenchymal stem cells, for example, can develop into specialized renal cells like nephrons and tubular Patients with CKD see advantages such as decreased creatinine levels after receiving stem cell transplants of epithelial cells and other types. Patients with chronic kidney disease (CKD) get an intravenous infusion of stem cells, which promptly move to the site of injury or inflammation and initiate the process of renal tissue regeneration. Furthermore, by para/autocrine signalling, these stem cells also induce/activate renal resident stem cells. ¹⁵

5) Lung Disease:

The following lung conditions are amenable to stem cell treatment:

I. Idiopathic pulmonary fibrosis (IPF):

characterized by lung fibrosis and scarring, IPF is an interstitial inflammatory condition that causes terminal pulmonary insufficiency and has an unclear ethology. Mesenchymal stem cell transplantation provides the following advantages to individuals with IPF disease:

a. Release cytokines that reduce inflammation to stop or reduce collagen deposition and persistent inflammation.

b. Differentiate the injured or damaged lung cells into lung progenitor cells in order to repair the lung tissue.

c. To stimulate or activate lung-based resident stem cells, use para/autocrine signalling.

d. The anti-apoptotic, immune-modulating, anti-inflammatory, and antifibrosis characteristics of mesenchymal stem cell transplantation enable this environment to support the cells perpetually, regulate their in vivo self-renewal and progeny production, or improve their ability to initiate host reparative processes.

ii. Chronic Obstructive Pulmonary Disease (COPD): This lungs illness includes both emphysema and chronic bronchitis. Cigarette smoking is the primary cause of COPD, one of the leading causes of death and disability worldwide. COPD forms: There are two primary types of COPD: One sign of "chronic bronchitis," a chronic inflammation of the bronchi (medium-sized airways) in the lungs, is a persistent, mucus-filled cough.

Due to its impairment in the ability of the smaller air sacs, called alveoli, to keep their functional form during exhalation, "emphysema" is referred to as an obstructive lung ailment. Emphysema is mostly caused by tobacco use, and long-term exposure to air pollution ages the lungs.¹⁶

6) Ischemia:

Medication-based approaches, surgical or endovascular revascularization treatments, such as coronary artery bypass graft (CABG) and angioplasty, and these procedures are currently the available treatment options for myocardial infarction and coronary arterial disease. However, the stem cell transplant in conjunction with angioplasty and CABG induces neo myogenesis and neo-vascularization. Since cardiac patients' muscle regeneration after angioplasty and CABG is an extremely difficult task in and of itself. When angioplasty is used, the coronary artery that was impacted by the infarct is transplanted with stem cells. New blood creation, muscle regeneration, and a decreased risk of recurrent heart attacks are the outcomes of this surgery.¹⁷

7) Rheumatoid arthritis (RA):

Steroids, methotrexate, cyclosporine, gold, and, more recently, infliximab (Remicade) is among the immune suppressive drugs now used to treat RA. These treatments may have short-term gains, but they have long-term detrimental effects because they indiscriminately compromise immunological responses. With different types of arthritis, stem cell treatment promotes therapeutic activity. In addition to promoting tissue repair in RA patients, stem cells particularly mesenchymal stem cells offer immunomodulation and initiate the production of anti-inflammatory cytokines to halt the immune system's assault on joint synovial fluid.

8) Coronary Arterial Disease:

Surgical or endovascular revascularization techniques, such as angioplasty and coronary artery bypass graft (CABG), are currently the primary therapies for coronary arterial disease and myocardial infarction. In addition to obstructing the main arteries, coronary artery disease results in the death of heart muscle, small blood vessels, and capillaries. On the other hand, angioplasty plus stem cell transplant results in neovascularization, which reduces the frequency of angina attacks. When bone marrow stem cells are injected using a balloon catheter during an angioplasty into the coronary artery that is related to the infarct, the process is known as neo-angiogenesis, or the development of new vessels. Bone Marrow Due to the fact that it includes all required regenerating cells and angiogenic growth factors, such as mononuclear cells.¹⁸

Non-therapeutic uses of stem cell research:

With the potential to treat or cure a wide range of human diseases, several companies and academic organizations are keen to explore the use of stem cells for nontherapeutic uses. The apps in question are designed to lessen the likelihood of harmful side effects like the growth of tumour’s and to avoid some of the difficult medical problems associated with diseases like diabetes and cancer. Adult stem cells are necessary for the recontouring of faces using a combination of the patient's own fat and stem cells. Furthermore, it seems that adding stem cells enhances blood flow to the skin, which enhances its appearance and may hasten the removal of aging collagen, which is believed to be a factor in the formation of wrinkles.

Maintaining a young appearance and healthy lifestyle has become increasingly important as people age. However, achieving a young appearance is no longer such a tough obstacle thanks to stem cell therapy. Stem cells are thought to have the ability to promote the growth of new skin cells, speed up the production of elastin, and accelerate the breakdown of aging collagen.¹⁹

Current Challenges and Future Possibilities:

Stem cells have a great deal of promise for cellular therapies, but their clinical and practical use is limited by a variety of ethical and technological issues. The primary obstacle to the clinical use of adult stem cells is the minimal number of cells that can be extracted from any adult tissue. Finding the cells and components in the so-called "stem cell niche" that affect the growth and differentiation of local adult stem cells may be one way to find a solution. For example, it is known that bone marrow stromal cells promote the growth and differentiation of HSCs in extended cultures.²⁰

The other tactic involves inserting genes that stop target cells from developing into the feeder layer of cells that supports them. It has been demonstrated that gene modification methods that upregulate notch ligands such as Jagged-1 and Delta in stromal cells stimulate stem cell growth without differentiation. Additionally, modified stem cells are a technique that is now under investigation. Improvements in our knowledge of the molecular mechanisms driving stem cell self-renewal and proliferation, along with the discovery of new genes regulating stem cell proliferation and differentiation, have led to the development of novel techniques. For example, it has been shown that early-expression genes that control several processes, including body part patterning, enhance the ability to self-renew. The annihilation of life in the form of an embryo has been a major ethical problem associated with the extraction and research of embryonic stem cells in various western nations. Combining pre-existing hESCs with an adult somatic cell is one way to circumvent the criticism and produce a cell line that retains the ESC's traits while retaining the somatic cell's genotype.²¹

CONCLUSION:

Medical experts believe that stem cell therapies have the power to change the trajectory of human disease and alleviate suffering. Although there are currently a number of stem cell therapies accessible, they are rarely used because the trials are usually costly and unproductive. The potential application of stem cells in the therapy of human illness is now partially seen. With the help of current advancements in science, patients with life-threatening and debilitating diseases will undoubtedly benefit from the therapeutic potential of stem cells in the near future.

The difficulty with stem cell therapy is not only stopping organ damage but also achieving cell engraftment with functional integration into the organ, stopping harmful tissue remodelling, and improving the function of the diseased organ. The expertise and knowledge of many different professions are needed to comprehend the underlying mechanisms and resolve the many unresolved issues concerning regeneration therapy. In any event, stem cell therapy is definitely on the rise for regeneration.

Medical experts predict that technology based on stem cell research will be employed in the future to cure a wide range of diseases and disabilities, such as cancer, spinal cord injuries, and muscle loss. In conclusion, stem cell therapy is the way of the future for regenerative medicine, but more research is needed to completely understand the biology of stem cells and their potential applications in medicine. The idea of stem cell-based therapies for human health is intriguing. It is undoubtedly quite enticing to have the chance to develop innovative stem cell-based medications in this rapidly developing sector.

REFERENCES:

1. Sachin Awasthi, R. N. Srivastava, Ajai Singh and Manoj Srivastav. Stem cell: past, present and future- a review article, Internet Journal of Medical Update. 2008; 3(1).

2. Roopa R Nadig. Stem cell therapy – hype or hope? A review. J Conserve Dent. 2009; 12(4).

3. Robert Lanza. Essentials of stem cell biology. 2007: 17-18.

4. Savneet Kaur, and Cckartha. Stem cells: concepts and prospects. Current Trends in Science. 436.

5. Elaine Fuchs and Srikala Raghavan. Nature Reviews Genetics. 2002; 199-209 doi:10.1038/nrg758.

6. Thomson et. Al. Blastocysts embryonic stem cell lines derived from human. Science. 1998; 282(5391): 1145–1147. Doi:10.1126/science.282.5391.1145.

7. Wang et al. Autologous bone marrow stem cell transplantation for the treatment of type 2 diabetes mellitus. Chin Med Journal. 2011

8. Xie et al. Human bone marrow mesenchymal stem cell differentiates into insulin-producing cells upon microenvironmental manipulation in vitro. 2009

9. Sun et al. Differentiation of bone marrow-derived mesenchymal stem cells from diabetic patients into insulin-producing cells in vitro. Chin Med Journal. 2007.

10. Salama et al. Autologous hematopoietic stem cell transplantation in 48 patients with end stage chronic liver diseases. Cell Transplant. 2010

11. Khan et al. Safety and efficacy of autologous bone marrow stem cell transplantation through hepatic artery for the treatment of chronic liver failure: a preliminary study. Transplant Proc. 2008

12. Thomas et al. Mesenchymal Stem Cells as Anti-inflammatories: Implications for Treatment of Duchenne Muscular Dystrophy. Cell Immunology. 2009

13. Helen et al. The New England Journal of Medicine). Cell Therapy for Muscular Dystrophy. 2008

14. Sen et al. Induction Therapy with Autologous Mesenchymal Stem Cells in Living-Related Kidney Transplants. JAMA. 2012

15. Tzouvelekis et al. Stem cell therapy for idiopathic pulmonary fibrosis: a protocol proposal. Journal of Translational Medicine. 2011.

16. Strauer et al. The acute and long-term effects of intracoronary Stem cell Transplantation in 191 patients with chronic heary failure: the STAR heart study. European Journal of Heart Failure. 2010

17. Rodriguez et al. Autologous stromal vascular fraction therapy for rheumatoid arthritis: rationale and clinical safety. International Archives of Medicine. 2012.

18. Dador (2010). Stem cells used to remove eye wrinkles http;//abclocal.go.com/kabc/story?section=news/health/ you healthandid=7351660

19. Sutherland H J, Eaves C J, Eaves A C, et al 1989 Blood 74 1563.

20. Hombria J C and Lovegrove B 2003 Differentiation71 461.

21. Cowan C A, Atienza J, Melton D A, et al 2005 Science309 1369.

Received on 07.02.2025 Revised on 10.03.2025

Accepted on 29.03.2025 Published on 03.05.2025

Available online from May 05, 2025

Asian J. Pharm. Res. 2025; 15(2):209-214.

DOI: 10.52711/2231-5691.2025.00034

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.