Stem cells are the body’s raw materials — the cells from which all other cells with specialized functions are generated. Under the right conditions in the body or a laboratory, stem cells divide to form more cells called daughter cells. These daughter cells either become new stem cells by self-renewal or become specialized cells by differentiation with a more specific function, such as blood cells, brain cells, heart muscle cells or bone cells. No other cell in the body has the natural ability to generate new cell types.

Stem cell research has picked up in the last decade. It assists in understanding the pathogenesis of diseases, drug trials and regenerative medicine. 

There are three main types of stem cells:-

• Embryonic stem cells
• Adult stem cells 
• Perinatal stem cells

The stem cells can be pluripotent or multipotent

Stem cell banking or preservation is the extraction, processing and storage of stem cells, so that they may be used for treatment in the future when required. The main sources of stem cells are – placenta, umbilical cord, bone marrow, amniotic fluid, menstrual fluid and adipose tissue.

Stem cell therapy, also known as regenerative medicine, promotes the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. It is the next chapter in organ transplantation and uses cells instead of donor organs, which are limited in supply. 

Researchers grow stem cells in a lab. These stem cells are manipulated to specialize into specific types of cells, such as heart muscle cells, blood cells or nerve cells. The specialized cells can then be implanted into a person. They have been employed to treat more than 80 haematopoietic, neuromuscular and degenerative disorders. Today, the only stem cell therapies that are approved by the FDA are those which use cells from the bone marrow or cord blood. These are being used to treat cancers of the blood and bone marrow. However, the FDA has other potential safety concerns for unproven treatments such as:

• Administration site reactions
• The ability of cells to move from placement sites and change into inappropriate cell types or multiply
• Failure of cells to work as expected, and
• The growth of tumours

FDA also cautions patients considering stem cell therapy as it does not govern treatment norms in many countries. Patients need to be fully informed about trials, their approvals and effects/side effects. 

Many challenges exist in stem cell research:

• More human pluripotent and multipotent cell research is needed since stem cell biology differs in mice and men
• The common feature of unlimited cell division shared by cancer cells and pluripotent stem cells must be better understood in order to avoid cancer formation
• The ability to acquire large numbers of the right cells at the right stage of differentiation must be mastered
• Specific protocols must be developed to enhance production, survival and integration of transplanted cells
• Clinical trials must be completed to assure the safety and efficacy of stem cell therapy. When it comes to stem cells, knowing they exist is a long way from using them therapeutically

 

FDA APPROVED DISEASES FOR TREATMENT USING UMBILICAL CORD BLOOD STEM CELLS

CHILDHOOD CANCERS – SOLID TUMORS Neuroblastoma Retinoblastoma Medulloblastoma

LEUKEMIAS Acute Lymphoblastic Leukemia (ALL) Acute Myelogenous Leukemia (AML) Acute Biphenotypic Leukemia Acute Undifferentiated Leukemia

CHRONIC LEUKEMIA Chronic Myelogenous Leukemia (CML) Juvenile Chronic Myelogenous Leukemia (JCML) Juvenile Myelomonocytic Leukemia (JMML) Chronic Lymphocytic Leukemia (CLL)

MYELODYPLASTIC SYNDROMES (sometimes called pre-leukaemia) Refractory Anemia Refractory Anemia with Ringed Sideroblasts Refractory Anemia with Excess Blasts Refractory Anemia with Excess Blasts in Transformation Chronic Myelomonocytic Leukemia (CMML)

LYMPHOMAS Hodgkin’s Lymphoma Non-Hodgkin’s Lymphoma (Burkitt’s Lymphoma)

OTHER DISORDERS OF BLOOD CELL PROLIFERATION Anemias Aplastic Anemia Congenital Dyserythropoietic Anemia Fanconi Anemia Paroxysmal Nocturnal Hemoglobinuria (PNH)  Inherited Red Cell (Erythrocyte) Abnormalities Beta Thalassemia Major (also known as Cooley’s Anemia) Diamond-Blackfan Anemia Pure Red Cell Aplasia Sickle Cell Disease Inherited Platelet Anomalies Amegakaryocytosis / Congenital Thrombocytopenia Glanzmann Thrombasthenia Inherited Immune System Disorders: Severe Combined Immunodeficiency (SCID) SCID with Adenosine Deaminase Deficiency(ADA-SCID) SCID which is X-linked SCID with absence of T & B Cells SCID with absence of T Cells, Normal B Cells Omenn Syndrome Inherited Immune System Disorders: Neutropenias Infantile Genetic Agranulocytosis (Kostmann Syndrome) Myelokathexis Inherited Immune System Disorders–Other Ataxia-Telangiectasia Bare Lymphocyte Syndrome Common Variable Immunodeficiency DiGeorge Syndrome Leukocyte Adhesion Deficiency Lymphoproliferative Disorders Lymphoproliferative Disorder, X-linked (also known as Epstein-Barr Virus Susceptibility) Wiskott-Aldrich Syndrome Myeloproliferative Disorders Acute Myelofibrosis Agnogenic Myeloid Metaplasia (Myelofibrosis) Polycythemia Vera Essential Thrombocythemia Phagocyte Disorders Chediak-Higashi Syndrome Chronic Granulomatous Disease Neutrophil Actin Deficiency Reticular Dysgenesis Cancers in the Bone Marrow Multiple Myeloma Primary Plasma Cell Leukemia (PCL) Secondary Plasma Cell Leukemia PCL) Waldenstrom’s Macroglobulinemia

INHERITED DISORDERS AFFECTING THE IMMUNE SYSTEM AND OTHER ORGANS Cartilage-Hair Hypoplasia Gunther’s Disease (Erythropoietic Porphyria) Hermansky-Pudlak Syndrome Pearson’s Syndrome Shwachman-Diamond Syndrome Systemic Mastocytosis

INHERITED METABOLIC DISORDERS Mucopolysaccharidosis (MPS) Storage Diseases Hurler Syndrome (MPS-IH) Scheie Syndrome (MPS-IS) Hunter Syndrome (MPS-II) Sanfilipp Syndrome (MPS-III) Morqui Syndrome (MPS-IV) Maroteaux-Lamy Syndrome (MPS-VI) Sly Syndrome, Beta-Glucuronidase Deficiency (MPS-VII) Mucolipidosis II (I-cell disease) Leukodystrophy Disorders Adrenoleukodystrophy (ALD) / Adrenomyeloneuropathy (AMN) Krabbe Disease (Globoid Cell Leukodystrophy) Metachromatic Leukodystrophy Pelizaeus-Merzbacher Disease Lysosomal Storage Diseases Niemann-Pick Disease Sandhoff Disease Wolman Disease Inherited Disorders–Other Lesch-Nyhan Syndrome Osteopetrosis

Success rates with stem cell therapy vary from disease to disease. However, due to the cost involved and FDA restrictions, few studies and data are available to understand the outcomes.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Stem Cells Indian Scenario

The National Guidelines for Stem Cell Research 2017 by the Indian Council of Medical Research (ICMR) provide that any stem cell use in patients, other than for hematopoietic stem cells (cells usually found in bone marrow, peripheral blood or umbilical cord blood) reconstitution for approved indications, is investigational. So, stem cell use in patients can only be as part of an approved and monitored clinical trial, and not therapy. Every use of stem cells in patients outside an approved clinical trial is deemed unethical and considered as malpractice.

But the guidelines are not legally enforceable and so many clinics provide stem cell treatments without putting the stem cell-related products through clinical trials. The Ministry of Health and the ICMR have argued for several years over rules on stem cells that could be exploited as a loophole and allow doctors to offer unproven and unregulated stem cell therapies.

The New Drugs and Clinical Rules, 2019 include stem cell-derived products without creating any exemptions for minimally manipulated stem cells, so it does not define stem cell-derived products. So, several clinics offer stem cell-based treatments that should be only allowed if they have the licences to continue their operations. Despite the law, some clinics continue as before with no licence.

References:

https://www.mayoclinic.org/tests-procedures/bone-marrow-transplant/in-depth/stem-cells/art-20048117

http://www.reelabs.com/stem-cell-therapy/what-is-stem-cell-therapy.html

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104807/

https://www.fda.gov/consumers/consumer-updates/fda-warns-about-stem-cell-therapies

https://www.imtj.com/articles/stem-cell-treatment-legal-india/

https://www.cordforlife.com/list-of-fda-approved-treatments/

https://bethematchclinical.org/transplant-indications-and-outcomes/additional-outcomes/older-patient-outcomes/