Cell Therapy in India
What is Regenerative Medicine? | Cell Therapy
Regenerative medicine is a newly evolving branch of modern medicine which refers to a process of replacing or regenerating cells, tissues or organs to restore their normal function. It involves cell therapy (cells); immunomodulation therapy (use of biologically active molecules) and tissue engineering (transplantation of organs or tissues grown in the lab). It works by stimulating the body's own repair mechanism to heal the irreparable tissues or organs. This could therefore potentially hold the key for addressing ailments which currently have no proven treatments or cures, such as, neurological disorders (spinal cord injury, cerebral palsy, brain stroke, muscular dystrophy, Alzheimer's disease, multiple sclerosis, autism, etc.), diabetes, cardiovascular disorders, bone disorders, hematopoietic disorders, cancers, hepatic, renal and dermatological disorders. Regenerative medicine will revolutionize surgical disciplines and is expected to become the gold standard of surgical procedures intended to activate and support the body’s natural healing.
- Self Renewal: where in the cells can divide indefinitely, while maintaining the undifferentiated state.
- Potency: where in the cells display the capacity to differentiate into specialized cell types.
cells can be classified into three broad categories, based on their ability to differentiate. Totipotent cells are found only in early embryos. Each cell can form a complete organism. Pluripotent cells can form any of the over 200 different cell types found in the body. i.e. they can regenerate an entire organ. Multipotent cells are derived from fetal tissue, cord blood and adult cells.
2. Different Types of Cells.
cells are classified as embryonic cells, umbilical cord cells and adult cells on the basis of their origin.
Adult cells are found in most organs of the human body and, depending on their origin they have different properties. They exist in several different tissues such as liver, bone marrow, adipose tissue, brain, etc. These cells are very versatile and can develop into many different cell types. The primary role of these cells is to initiate the repair process in the organ following an injury. Unlike embryonic cells, the use of adult cells is not considered to be controversial and do not have any ethical issues, as they are derived from adult tissue samples rather than destroyed human embryos.
Umbilical Cord Cells:
Umbilical cord blood cells are obtained from the umbilical cord immediately after birth. These cells are also referred to as neonatal cells and are less mature than those cells found in the bone marrow of adults or children. It is a rich source of hematopoietic and non-hematopoietic cells. Among others, it contains endothelial cells, mesenchymal cells, etc. The advantages of using cord blood cells are that they can be procured non-invasively are available in abundance and does not produce strong graft-versus-host disease. In several countries around the world, cord blood is collected and either banked in public banks for general use, or stored by private companies for private use, in private cord blood banks. There have also been reports that the matrix cells from the umbilical cord (Wharton's jelly) contain potentially useful cells.
Embryonic cells are derived from the early stage embryo (5-7 day embryo) known as the blastocyst stage, which are obtained from the IVF clinics. Their most remarkable feature is their ability to retain the developmental capacity to generate all functional adult cell types. These cells have the ability to divide indefinitely as well as to differentiate/transform in all fetal and adult cells and their mature forms. The availability of these cells makes them useful for cell transplantation that may be applicable to a wide range of human ailments. But, these cells also have a tendency to form tumors called as teratomas, which is their major disadvantage. Currently, due to this reason, the use of these cells is restricted to research only. Apart from scientific issues, the embryonic cells also have ethical issues and controversies regarding use of live embryos for deriving or making these cells.
Adult cells are currently the most practical and workable option for many diseases and can be easily obtained from the same patient.
3. Benefits of Adult Cells
Adult cells have the following benefits:
- They are available in abundance and can be isolated easily.
- They are isolated from patients, which overcomes the problem of immunological rejection.
- Adult cells have the potential to replenish many specialized cells from just a few unspecialized ones.
- They do not have any ethical issues as they do not involve destruction of embryos.
- The risk of tumor formation is greatly reduced as compared to the use of embryonic cells.
4. Where are adult cells found?
Adult cells are found from the following sources:
i. Bone Marrow
Bone marrow is the most accessible and most studied source of adult cells. Different types of cells are found to be present in the bone marrow, which differ in their potential to differentiate and form cells from one or more germ layers. It contains hematopoietic and mesenchymal cells. They are more plastic and versatile because they are multipotent and can be differentiated into many cell types both in vitro and in vivo. Bone marrow cells have been reported to contribute to angiogenesis, somatic muscle development, liver regeneration, and the formation of central nervous system cells.
ii. Gut cells:
The gastrointestinal epithelial lining undergoes continuous and rapid renewal throughout life. Differentiation thus exists in specific areas of the tract. Epithelial cell renewal in the intestine is sustained by multipotent cells. The cell hierarchy in the gut and the fact that cells and their progeny are located in well defined units make the gut an ideal in vivo model for cell research.
iii. Bone and cartilage cells:
Mesenchymal Cells in bone marrow can differentiate into bone and cartilage under appropriate conditions. If, bone or cartilage is injured, there are cells inherent in bone or cartilage to participate in the repair process. Bone itself has been found to have both uncommitted cells as well as committed ones. In addition, when bone is fractured, there is exposed marrow and abundant bleeding with hematoma formation in the marrow space, which results in good repair potential. On injury to cartilage, cells do participate in the repair process. However, they are in small numbers and the regulatory factors are limited. It is postulated that these cells may be derived from surrounding tissues such as muscle, bone or other non-cartilaginous tissues.
iv. Epidermal cells (skin and hair):
Human skin consists of the outer epidermis and inner dermis. Hair and sebaceous glands also make up the epidermis. The epidermis houses cells at the base of the hair follicle and their self-renewing properties allow for the re-growth of hair and skin cells that occurs continuously.
v. Neural cells:
Neural cells are found in the adult brain. Alternately, sources of neural cells are olfactory mucosa cells, skin, adipose tissue, Schwann cells, etc. Currently, neural cells are being explored since they are known to have a potential to treat incurable neurological disorders. Neural cell lines have been established and being tried in clinical trials for safety and efficacy.
5. Benefits of using Bone Marrow Derived Mononuclear cells (BMMNCs)
cells harvested from bone marrow is one of the earliest sources and has been used widely for diseases/disorders of blood.
Sibling/allogenic (related/matched donors) bone marrow transplantation for leukemia, thalassemia, sickle cell anemia, has been used as standard medical practice for more than 150 years now.
When the blood compartment is not diseased, cells from bone marrow is a very easy and replenish able source of cells. It has been widely studied and researched. Hence, we know about its characteristics and what it can do very thoroughly. The bone marrow is composed of various different fractions of cells, each having its own function and role. These fractions are haematopoietic cells, mesenchymal or stromal cells, very small embryonic like cells, endothelial cells. Since, each of these have a different function, a cocktail of these cells, has a combinatorial action and hence more effective than infusion or transplantation of a single type of cell (eg. Mesenchymal cell alone).
a) Haemopoietic cells: The bone marrow is rich in these cells which stimulate the formation of new blood vessels, release chemicals which are favorable for repair & regeneration and promote functional & metabolic improvement.
b) Mesenchymal cells (Multipotent Mesenchymal Stromal Cells): These are multipotent cells that have the potential to differentiate into multiple lineages including bone, cartilage, muscle, tendon, ligament fat, nervous tissue or brain tissue and a variety of other connective tissues. These also contribute to angiogenesis, somatic muscle development, liver regeneration and the formation of central nervous system cell types.
c) Multipotent Adult Progenitor Cells (MAPC) d) Marrow-isolated adult multilineage inducible (MIAMI) cells e) Multipotent Adult Cells (MACS) and f)Very Small Embryonic Like (VSEL) Cells are newer fractions being found in the bone marrow, which further contribute to the effectiveness of the bone marrow derived cells and are considered to be pluripotent (can form a wide range of cell types).
How do cells work?
cells are actively involved in the formation of new tissues and thereby promote repair and regeneration. When injected, these cells migrate to the damaged areas of the tissue due to the release of chemical signals and they further fuse with those tissues and help in regeneration. The mechanisms of functioning that cells display can be noted down as follows:-
- Homing: Once the cells are injected they have a unique ability of “homing” or migrating into the site of injury to carry out the repair process.
- Transdifferentiation: These cells can multiply and form the cells of the same tissue or form cells of a completely different tissue. Cells differentiate independently or by fusing with the resident cells.
- Paracrine activity: cells produce various chemical factors which activate the resident cells and stimulate them to carry out repair of the damaged tissue.
- Increasing angiogenesis: cells help in forming new blood vessels. This increases the blood circulation and oxygen supply in the body. This either takes place as the cells differentiate and form new tissues or by paracrine activity which indirectly enhances angiogenesis.
- Immune regulation:cells release factors which help regulate the affected immune system and decrease inflammation.
NeuroGen Brain and Spine Institute takes care of patients affected with incurable neurological disorders. Our aim is to provide complete treatment & rehabilitation to these patients and help them become as independent as possible. For this, a specialized treatment known as cell therapy is used. In addition, the patient is treated as a whole and all of his/her problems addressed, so as to facilitate overall rehabilitation and independence.
Consultation with specialists at NeuroGen Brain and Spine Institute can be done by the following ways:
- In person: Out-patient Department at NeuroGen is generally active from Monday to Friday with prior appointments. Telephonic appointments can be made at 0091 22 27704739/27713018
- Telephonically: Doctors at NeuroGen are available to speak to the patients or patients relatives –Monday to Saturday (from 10am to 5 pm).
Treatment schedule at NeuroGen is typically for 7 days, which includes cell therapy followed by holistic neurorehabilitation (physiotherapy, occupational therapy, speech therapy, psychological counseling, urorehabilitation, sexual rehabilitation, bedsore management, etc.)
Once the date for cell therapy has been decided, the patient will need to undergo a battery of tests for 2 purposes:
- To ensure preoperative fitness: Routine blood tests, such as CBC, Blood sugar, S creatinine, S electrolytes, LFT, CT, BT, PT, HIV I and II antibodies, HbsAg, HCV antibodies.
- To assess severity and nature of the disease/disorder (as required): special imaging tests such as MRI Brain, spine, musculoskeletal system, PET CT Scan brain, CT Scan spine; Electrophysiological tests such as EEG, EMG, NCV, SSEP, VEP, BERA; other special tests if required.
Administration of cell stimulating factors: Granulocyte Colony Stimulating factor (Grafeel/XPHIL) has to be administered 48 hrs and 24 hrs before bone marrow harvesting is done.
The broad schedule is as follows:
Day 1: Complete pre-operative assessment
The patients are assessed neurologically, physically, functionally, psychologically along with a pre-anaesthetic workup.
Apart from assessment, treatment strategy for each patient is planned out. This includes:
- Assessment of muscle power and function and charting out of motor points on the muscles, where cells have to be injected. This is done by the rehabilitation specialists
- Setting of short term and long term goals for the patient, based on current condition and expected progress or improvement after the cell therapy. This is done by the medical and rehabilitation team as a whole.
Day 2: cell therapy
The cell therapy process using autologous (taken from the patient’s own body) bone marrow derived cells consists broadly of 3 stages.
cell therapy is done in 3 steps:
(1) Procurement of the cells from the bone marrow via a bone marrow aspiration in the operating theatre
This is done through a bone marrow aspiration needle, which is a thin needle inserted into the hip bone. Procedure is usually done under local anaesthesia. For children who are non cooperative and adults who cannot tolerate the procedure, sedation or general anaesthesia as required is administered. Procedure takes 15mins to 30 minutes. Between 80ml to 120ml of bone marrow is aspirated, depending on the weight of the patient. Patient is sent back to the room for about 3 to 3 and a half hours.
Aspiration of Bone marrow
(2) Separation, harvesting, enriching &/or expansion and differentiation in the laboratory
cells are separated in the laboratory.
Separation of cells in the Laboratory
Separated Stem Cells
(3) Transplantation or delivery of the cells to the desired location.
Once cells are separated and purified (in about 3-3 ½ hrs), patient is taken back to the operation theatre. Injection of cells into the fluid around the brain and spine (intrathecal injection) is carried out using either an epidural needle (portex) or a spinal needle. Cells are first diluted in the CSF and then injected into the spinal space. In certain patients where cells are to be injected into the muscles, (eg. Muscular dystrophy patients – as assessed and recommended by the rehabilitation team) these cells are diluted in the CSF and then injected into the muscles using a very thin needle.
Injection of the isolated cells (fig3a, 3b,3c):
Post treatment care: Following the cell therapy, patient is required to be lying down for the day and drink plenty of fluids, to prevent, ”spinal headache”.
From the very next day, patient is started on an intensive rehabilitation regime, which is customized to the patient requirement.
Day 3-6: REHABILITATION THERAPY
Rehabilitation is an integrated approach which aims to transform a disabled person into a “differently abled person”. To accomplish this we have a team comprising of physiotherapist, occupational therapist, speech therapist, neuro-psychologist, urologist, andrologist, and neuro-physician.
Though the rehabilitation protocol is designed separately for each patient, the broad outline and aims are as given below.
- To assist in movement restoration
- To increase muscle strength, endurance, coordination & balance.
- To reduce spasticity & increase joint range of motion & prevent contractures.
- To assist in gait training with or without ambulatory aids.
- To perform pulmonary rehabilitation including breathing exercises, in order to reduce fatigue & keep lungs clear.
- To evaluate & train the patient in self care activities such as dressing, eating, bathing & personal hygiene to maximize independence.
- To evaluate & train the patient to compensate for sensory & perceptual deficits taking personal, social & cultural tastes into consideration.
- To aid in home evaluation and recommend steps to make the environment barrier free & accessible.
- To provide holistic training in home management skills, using simpler methods or aids to minimize fatigue and conserve energy.
- To reduce psychological distress.
- To enhance and promote psychological wellbeing.
- To use testing tools or scales which measure the objective scores of some psychological domains or cognitive domains.
- To use therapies and counseling techniques thereby enabling clients to make positive changes in their lives.
- Behavioural therapy: it involves a complete understanding of the child’s behavior and changing the behavior to reduce dysfunction & improve the quality of life. This can be done by encouraging desired behavior and eliminating undesired behavior.
Speech Therapists are specially trained in exercises to improve clarity of speech, sound production, speech development and strengthening of the voice. They also educate about techniques to improve swallowing and avoid choking spells.
They focus on various components as follows
- Speech- includes phonation, articulation, fluency, resonance and voice
- Language development- deals with comprehension and expression in oral, written, graphics and signs
- Cognitive aspects of communication– focuses on attention, memory, problem solving, executive function
- Swallowing – for solids & liquids
Assessment and Advice by the Urologist
Patients of spinal cord injury, multiple sclerosis, cerebellar ataxia, dementia and others who have problems with bladder or bowel continence are provided with a specialist/urologist’s consultation.
- To help the patients to overcome their bladder and bowel problems if any.
- To perform a detailed evaluation of the bladder capacity, through urodynamic study and to advise necessary treatment, if required.
- To make patients independent in personal hygiene by teaching them self intermittent catheterization and self evacuation, as far as possible.
Assessment and advice by Andrologist /Sexual rehabilitation expert:
Patients who have sexual issues as a part of their neurological deficit (for eg. spinal cord injury) can take counseling from a sexual rehabilitation expert.
- To evaluate/assess for sexual dysfunction, either due to the disorder or due to physical limitations.
- To advise remedies, both in terms of medications and practicalities.
- To counsel regarding misconceptions and provide correct information.
Other problems associated with the neurological disorders such as bed sore management, cardiac problems (in the case of muscular dystrophy), psychiatrist consultation, chest physician, etc. are also addressed.
Creative Visualization workshop or motivational workshop
- To motivate patient to set goals for themselves (long term and short term)
- To guide them how to work towards these goals, in a step wise manner and reach them
- To harness their positive energy & cement the therapy as a whole through mind power techniques and meditations to awaken the subconscious mind.
The workshop includes:
- Guided imagery
- Inspirational stories
- Patient videos
- Goal setting
- Creative visualization
- Group therapy
Life is an opportunity, benefit from it.
Life is beauty, admire it.
Life is a dream, realize it.
Life is a challenge, meet it.
Life is sorrow, overcome it.
Life is a song, sing it.
Life is a struggle, accept it.
Life is a tragedy, confront it.
Life is an adventure, dare it.
Life is too precious, do not destroy it.
Life is life, fight for it.
― Mother Teresa
Inclusion of a therapeutic practice like yoga, in tandem with physiotherapy & occupational therapy can help mitigate the conditions of debilitating & degenerative diseases and greatly improve the quality of life. Yoga therapy uses asanas that involve stretching and relaxation of various muscles in combination with deep breathing techniques to improve muscle tone and reduce pain. Research shows that the benefits of yoga for movement disorders include improved strength, flexibility, balance, overall fitness and quality of life.
Yoga also addresses the mental and emotional damage caused by the illness. It helps to infuse positive energy into the individuals and thus help them to increase their inner strength to fight off depression & anxiety that characterize such illnesses. It instills a sense of hope into these patients.
Healthy diet is the basis on which stands the tower of any treatment. Every patient will be evaluated by our expert dietician and according to individual requirements, a personalized diet chart will be recommended.
After cell treatment, patients have to follow a regular exercise program, requiring a lot of energy, which is obtained from good diet. E.g
-Many patients are anemic resulting in easy fatigability, so they need high iron diet.
-To rebuild muscles we need high protein diet.
-Obesity may cause restricted activities, thus requiring low fat, low carbohydrate diet etc.
All these issues are taken into consideration along with local availability, cost of food; cultural, social, religious norms and staple diet of the patient.
Day 6: DISCHARGE
After a final session of rehabilitation, the patient is given advice to be followed for the next few months and discharged from the hospital.
A follow-up appointment is scheduled at regular 3 month intervals to track the patient’s progress.
Every patient becomes a part of the NeuroGen family. We strive to provide holistic care for all members and ensure that we extend support to them even after the treatment.