What is regenerative medicine?
As the name suggests, regenerative medicine is a medical discipline based on treatments involving regenerating or restoring functions of cells/tissue/organs damaged by disease or injury. It is a multidisciplinary field that aims to restore, repair, or replace damaged or diseased tissues and organs by using biological materials, such as cells, biomolecules, and scaffolds. It combines principles of biology, engineering, and medicine to develop innovative approaches for treating a wide range of conditions that currently have limited or no effective treatment options.
There are several key approaches and strategies within regenerative medicine:
- Cell based therapy: This involves the transplantation or introduction of cells, such as stem cells or progenitor cells, into damaged tissues or organs to promote regeneration.
- Tissue enginering: Tissue engineering combines cells, biomaterials, and bioactive molecules to create functional tissue substitutes in the laboratory.
- Biomaterials and Scaffolds: These materials can mimic the natural extracellular matrix and provide physical and biochemical cues to guide cell behavior and tissue development.
- Gene Therapy: Gene therapy involves the introduction of genetic material into cells to modify their function or behavior.
- Secretome: Stem cell secretome includes small molecules and biologics. Regenerative medicine also explores the use of small molecules, growth factors, cytokines, and other biologically active substances to stimulate the body's own regenerative processes.
Why are hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) the most used stem cell type?
HSCs and MSCs ae among the most extensively studied and used types of stem cells for several reasons:
- Well characterized stem cell types that provides based to the knowledge and properties and hence their usesage.
- Abundance: Both the celsl types are presently abudnantly in various tissues like bone marrow, cord blood, and peripheral blood. MSCs can be isolated from almost 20 types of tissues of our body.
- Established clinical applications: HSCs are the only stem cells approved for routine clinical practice. The ability to safely obtain them from venous and umbilical cord blood is an essential factor contributing to their high degree of usage.
- Low immunogenicity: Both HCS and MSCs are less likely to be recognized and rejected by the immune system when transplanted into a recipient. This characteristic reduces the need for immunosuppressive drugs and improves the feasibility of allogeneic transplantation.
- Tissue repair and regneration potentials: HSCs and MSCs have promising potential for tissue repair and regeneration due to their ability to differentiate into various cell types. Additionally, MSCs secrete a variety of growth factors and cytokines that promote tissue healing.
Why do some researchers use embryonic stem cells when induced pluripotent stem cells (iPSCs) can work exactly like them?
Although it is now well-established that iPSCs have essentially equivalent cellular properties as ESCs, some investigators still express concern because they are not identical. Several reasons can be assigned why resarchers still use ESCs in place of iPSCs;
- Greater understanding of ESCs protcol: ESCs have been studied for a longer period of time, and robust protocols have been developed for their culture, expansion, and differentiation into various cell types.
- Validation and comparison: ESCs serve as a gold standard for evaluating the properties and behavior of iPSCs. Depending upon the methodolgoy utilized for generation of iPSCs, properties of ESC-like cells may differ.
- Research continuity: Many researchers have existing research lines and data using ESCs, and it may be more practical to continue using ESCs in their ongoing studies rather than transitioning to iPSCs.
- Disease modeling: In certain cases, researchers may find it advantageous to use ESCs derived from embryos carrying specific genetic mutations
- Abnormality: The production of iPSCs may also introduce abnormalities that do not occur in naturally produced ESCs. However, thus far, no differences have been described that are prohibitive to the use of iPSCs in the ways in which ESCs might be used to develop therapeutics.
It’s important to note that iPSCs offer significant advantages over ESCs in terms of ethical considerations since they can be generated from adult somatic cells without the need for embryo destruction. Moreover, iPSCs also allow for the creation of patient-specific cell lines, which can be valuable for disease modeling, personalized medicine, and drug development.
Many clinics that deliver stem cell-based therapies claim to have conducted clinical research or trials or provided testimony of patients who have been cured due to the stem cell therapy provided at their facility. How reliable are these tests, research, and testimony?
While there have been significant advancements in stem cell research and therapies, it is important to approach claims and testimonials with a critical mindset. The reliability of stem cell treatments and testimonials can vary greatly and requires careful evaluation. Here are some key considerations:1) Scientific evidence, 2) Regulation and approval, 3) Patient testimonials, and 5) Transparency and clarity.
It is important to note that some clinics may offer unproven or experimental stem cell treatments that lack scientific evidence. These treatments may carry risks and may not deliver the claimed benefits.
What are the stem cell biomarkers?
Stem cell bomarkers are the specific molecules or characteristics that can be used to identify and isolate stem cells from other cell types. Here are some commonly used stem cell biomarkers:
- Cell Surface Markers: These are proteins or antigens present on the cell surface that can be detected using antibodies. They are often plasma membrane proteins but can also be expressed in other cellular compartments (e.g., nuclear biomarkers). These expressed proteins are the indicators used to detect stem cells among similar-appearing differentiated cells and progenitor cells. Biomarkers for ESCs are true “stem cell biomarkers”, as they only identify ESCs (or iPSCs). However, the term “stem cell biomarker” is a misnomer for adult stem cells (ADCs) because progenitor cells produced by ASCs also express them. ASC detection analyses with single biomarkers have poorer specificity than analyses with multiple biomarkers like CD34, CD90, CD105, and CD133.
- Transcription Factors: Transcription factors are proteins that regulate gene expression and play crucial roles in maintaining ‘stemness’ of a stem cell. Nuclear expresson of proteins such as Oct4, Sox2, and Nanog are well-known transcription factors associated with pluripotency in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs).
- DNA Methylation Patterns: DNA methylation, an epigenetic modification, can be used as a biomarker to distinguish between differentiated cells and stem cells.
- Enzymes and Cytoplasmic Markers: Alkaline phosphatase is often used as a marker for undifferentiated pluripotent stem cells. Intracellular markers such as SSEA-1 and TRA-1-60 are also used to identify pluripotent stem cells.
- Functional Assays: Functional assays test the ability of cells to form specific tissue structures in vitro or in vivo, or evaluating their capacity for multilineage differentiation.
What is the appropriate dosage for stem cell treatments?
Determining the appropriate cell dosage is crucial for achieving desired therapeutic outcomes and ensuring the safety and effectiveness of the treatment. The optimal cell dosage can vary depending on several factors, including the type of stem cells used, the specific condition being treated, the route of administration, and individual patient characteristics. In some cases, the appropriate cell dosage may be based on established guidelines or protocols developed for specific stem cell therapies.. MSC-containing preparations, 1-10 million total cells per kilogram of body weight per dose treatment are generally recommended. For HSCT, the minimal dosage is 3 million CD34-expressing cells per kilogram of patient body weight.
It’s important to note that the optimal cell dosage is an ongoing area of research and may vary based on evolving scientific evidence and clinical experience. Too few cells may not have a significant therapeutic effect, while too many cells may lead to complications such as immune reactions or abnormal cell growth.
What are the significant challenges of stem cell treatment?
- Expansion: Need for a sufficient number of stem cells for application. However, tissue contains a small number of stem cells. Scaling up the production of stem cells to meet the demand for large-scale therapies remains a challenge. Culturing sufficient quantities of stem cells while maintaining their quality and potency is crucial.
- Differentiation Control: A propensity of stem cells for the production of differentiated cells in a regulated manner is often challenging. Ensuring that stem cells differentiate into the desired cell type and function properly is crucial for successful outcomes.
- Quantification of Stem Cells: Quantification of stem cell population among mixed cells is still challenging. No technologies, thus far, have been available for counting ‘true’ tissue-specific stem cells,, thereby poses challeng to outcomes. Kinetic stem cell counting from Asymmetrex® provides real and accelerated methodology for coutning ‘true’ stem cells. An advanced Rabbit Count Algorithms for rapid counting of tissue stem cells and TORTOISE Test allow monitoring of specific tissue stem cell number during expansion culture (https://asymmetrex.com).
- The Correct Dose: Due to inaccurate specific cell counting, the dosage of stem cells remains insufficient. In the case of Hematopoietic stem cell transplantation (HSCT) with bone marrow-derived cells and peripheral blood cells, there is the possibility of excessive dosing with scarce donor samples.
- Safety Concern: Ensuring the safety of stem cell treatments is of utmost importance. Stem cells have the potential to form tumors or differentiate into unintended cell types, posing risks to patients.
- Immune Rejection: Receiving stem cells from a donor, a risk of immune rejection by the recipient's immune system may be detrimental to the desired outcomes. Immunosuppressive drugs may be required to mitigate this risk, which can have their own side effects and complications.
- Standardization and Quality Control: Developing standardized protocols for stem cell isolation, culture, and administration is essential. Consistency in cell quality, potency, and dosage is crucial to achieving predictable and reproducible therapeutic outcomes.
- Ethical Consideration: The use of certain types of stem cells, such as embryonic stem cells, raises ethical concerns due to the destruction of embryos. Striking a balance between scientific progress and ethics remains a challenge for stem cell research and therapy.
- Cost of Stem Cell Treatment: Stem cell treatments can be expensive, limiting their accessibility to a broader population.
- Long-term Efficacy and Durability: While short-term benefits of stem cell treatments have been observed in certain conditions, the long-term efficacy and durability of these therapies remain a challenge.
- Public Perception and Education: Public perception and understanding of stem cell treatments can influence their acceptance and accessibility.
Are there techniques available to determine the treatment dosage specific to stem cells?
Yes, there are several techniques available to determine the treatment dosage specifically for stem cells. These techniques include but are not limited to flow cytometry, colony-forming unit assays, immunohistochemistry, and quantitative polymerase chain reaction (qPCR) analysis. These methods help in quantifying the number of stem cells present and evaluating their response to different treatment dosages, allowing for more precise and targeted therapeutic interventions. The number of stem cells per dose for the treatment differs and is decidedly imperative for maximum response While there is no standardized method specifically designed for this purpose, several approaches are employed to estimate the appropriate stem cell dosage. Various approaches are employed to estimate the appropriate dosage of stem cells. These approaches include preclinical studies, in vitro experiments, animal models, and clinical trials. Preclinical studies involve laboratory investigations to assess the safety and efficacy of different stem cell dosages. In vitro experiments utilize controlled cell cultures to study the response of stem cells to varying doses of treatments. Animal models provide valuable insights into the dosage response of stem cells in living organisms. Finally, clinical trials involving human subjects help determine the optimal stem cell dosage through careful monitoring and evaluation of therapeutic outcomes.
The basis for stem cell treatment dosage is either total number of cells utilized or biomarker fractions like CD34+ cells for HSCT. In the case of HSCT, two methods could be used to provide the HSC-specific dosage. The first, available for about two decades, is the SCID mice repopulating cell (SRC) assay. However, technically prohibitive features of the SRC assay made it impractical for routine clinical use. A second, more recently developed method, called kinetic stem cell (KSC) counting, is still in development and not yet certified for clinical use.
What are the tissue-specific stem cells?
They are also referred to as somatic stem cells or adult stem cells. Tissue-specific stem cells are present in perinatal tissues and the postnatal body. These stem cells have the ability to self-renew and differentiate into specific cell types within their respective tissues. Here are some examples of tissue-specific stem cells: hematopoietic stem cells, mesenchymal stem cells, neural stem cells, epidermal stem cells, intestinal stem cells, mammary stem cells, hepatic stem cells and stem cells of other tissue origins. Each type of stem cell has its own unique characteristics and functions within its specific tissue environment. Tissue-specific stem cells produce a limited set of specialized cells and have limited potency, unlike ESCs and iPSCs. They also differ from ESCs and iPSCs by producing differentiated cells by asymmetric self-renewal divisions.
Can tissue-specific stem cells be utilized in regenerative medicine?
Yes, tissue-specific stem cells are even the preferred for regenerative medicine. Due to the inherent capabilities of asymmetric self-renewal, tissue-specific stem cells provide cells for growth and repair and maintain their resident stem cell populations. An insufficient number of tissue-specific stem cells limit their application in regenerative medicine.
Can stem cells of one patient be transferred to another patient?
No, stem cells from one patient cannot be directly transferred to another patient without significant complications. Stem cell transplantation or transfer typically involves two types: autologous and allogeneic.
Autologous Stem Cell Transplantation: In this type, stem cells are collected from the patient's own body, usually from their bone marrow or peripheral blood. These cells are then stored and later reintroduced into the same patient after undergoing necessary treatments or procedures.
Allogeneic Stem Cell Transplantation: In allogeneic transplantation, stem cells are obtained from a donor who is a close genetic match to the recipient. This is usually a family member or an unrelated donor. Allogeneic transplantation carries the risk of graft-versus-host disease (GVHD). To minimize GVHD, a close match between the donor and recipient is necessary, typically determined by human leukocyte antigen (HLA) matching.
In pet animals like dogs, allogeneic mesenchymal stem cells are safe to inject and found proven therapeutic effects in many incurable and chronic diseases. It is imperative to mention that MSCs derived from dogs have a reduced capacity to stimulate immune responses compared to other cell types. This low immunogenicity can be attributed to several factors: 1) low expression of major histocompatible complex (MHC) molecules, 2) Lack of co-stimulatory molecules and 3) Production of immunomodulatory factors like interleukins, prostaglandins, and indoleamine 2,3-dioxygenase (IDO), which can suppress immune responses.
Where does India stand in stem cell treatment?
India has made significant advancements in the field of stem cell treatment and research. It has emerged as a notable destination for stem cell therapies due to several factors:
- Regulatory Environment: India has established guidelines and regulations for stem cell research and therapy to ensure ethical practices and patient safety. The Indian Council of Medical Research (ICMR) and the Department of Biotechnology (DBT), New Delhi, both have provided guidelines for stem cell research and clinical trials.
The national guidelines for stem cell research in India can be accessed through https://dbtindia.gov.in/sites/default/files/National_Guidelines_StemCellResearch-2017.pdf
- Clinical Expertise: India boasts a pool of skilled healthcare professionals, including doctors and researchers, who specialize in stem cell treatments. Many medical institutions and hospitals in India have dedicated stem cell research and therapy centers, equipped with advanced technologies and expertise. In veterianry science, few institutions like Centre for Stem Cell Research and Regenerative Medicine at Madras Veterinary Collge, Chennai, Indian Veteriarny Resaerch Institute, and Animal Stem Cells Lab at GADVASU have research and clinical expertise in persuing stem cell research in animals.
- Diverse Stem Cell Applications: India has been actively exploring stem cell applications across various medical fields, including regenerative medicine, orthopedics, cardiology, neurology, ophthalmology, and more.
- Medical Tourism: India has become a popular destination for medical tourism, including stem cell treatments.
- Research and Collaboration: Indian scientists and researchers are actively involved in stem cell research and collaborating with international institutions and experts. This fosters knowledge exchange, promotes innovation, and contributes to advancements in the field.
However, it is important to note that while India has made progress in stem cell treatment, the field is constantly evolving, and individual treatment outcomes may vary. The field of animal stem cell treatment in India is steadily growing and evolving. While the use of stem cells in veterinary medicine is relatively newer compared to human medicine, there has been an increasing interest and adoption of stem cell therapies for animals in India.
Where can I learn more about the applications of stem cells in animals?
To learn more about the applications of stem cells in animals, you can explore the following resources:
- Veterinary Research Journals: Many scientific journals publish research articles and studies related to stem cell applications in veterinary medicine. Some notable journals include Veterinary Surgery, Veterinary and Comparative Oncology, Journal of Veterinary Internal Medicine, and Stem Cell Research & Therapy.
- Books: A comprehensive book dedicated to stem cells in veterinary science can be found here https://link.springer.com/book/10.1007/978-981-16-3464-2 .
- Veterinary Conferences and Symposia: Attending conferences and symposia focused on veterinary medicine and regenerative therapies can provide valuable insights into the applications of stem cells in animals. Such conferences include the World Congress on Veterinary and Animal Science and the International Veterinary Regenerative Medicine Symposium.
- Veterinary Universities and Research Institutions: Various veterinary universities and research institutions conduct studies and clinical trials related to stem cell therapies in animals. University of Veterinary Medicine Vienna, University of California, Davis School of Veterinary Medicine, and Cornell University College of Veterinary Medicine can offer valuable information and research findings.
- Veterinary Regenerative Medicine Courses: Some institutions and organizations offer specialized courses and training programs on veterinary regenerative medicine and stem cell therapies. These courses can provide comprehensive knowledge and hands-on training in the field.
In India, following institutions provide stem cell therapy courses or training programs: 1) StemRx Bioscience Solutions: StemRx Bioscience Solutions is a stem cell research and training organization based in Mumbai. 2) Institute of Stem Cell Biology and Regenerative Medicine (inStem), located in Bangalore, is an autonomous institute under the Department of Biotechnology, Government of India. They offer Ph.D. and integrated Ph.D. programs in stem cell biology and regenerative medicine. 3) International Institute of Stem Cell Science and Regenerative Medicine (IIScR): IIScR, based in Bangalore, offers a range of programs in stem cell science and regenerative medicine.4) National Centre for Cell Science (NCCS): NCCS, located in Pune, Maharashtra, is an autonomous institute under the Department of Biotechnology, Government of India. They offer a Ph.D. program in stem cell biology and regenerative medicine and 5) Centre for Stem Cell Research (CSCR): CSCR, situated in Vellore, Tamil Nadu, is a research and training center dedicated to stem cell biology and regenerative medicine. They offer a comprehensive Ph.D. program in stem cell science.
Does India have guidelines for stem cell research?
Yes, in medical science, India drafted the first guidelines in 2007 for the scientists and clinicians working in the field of stem cells called National Guidelines for Stem Cell Research (NGSCR). The policies were further updated in 2017.
In veterinary science, as of my knowledge till March 2022 (DOI: 10.56093/ijans.v92i5.115586), there is no specific comprehensive guideline exclusively dedicated to stem cell research and therapy. However, different countries may have their own regulations and guidelines for veterinary stem cell research and therapy. The regulatory framework for stem cell research and therapy in veterinary science is still developing. The Indian Council of Agricultural Research (ICAR) and the Veterinary Council of India (VCI) have provided some guidelines and regulations for veterinary stem cell research and therapy. However, these guidelines may not specifically focus on stem cell therapy but rather cover broader aspects of veterinary practice and research.
Who monitors stem cell research in India?
Two levels of monitoring systems- national and institutional- exist in India. At the national level, it is the National Apex Committee for Stem Cell Research and Therapy (NAC-SCRT). At the Institutional level, it is the Institutional Committee of Stem Cell Research (IC-SCR). For the clinical trials of stem cells and their products as "drugs," permission from the Cell Biology Based Therapeutic Drugs Evaluation Committee (CBBTDEC) of the Central Drugs Standards Control Organization is mandatory.
