Introduction
Current challenges in developing effective stem cell therapy
Heterogeneity and inherent differential potency of stem cells
Heterogeneity of disease progression
Homing and targeted stem cell delivery
Complexity of mechanism of action of cell therapy
Hypothesis
Strategies to increase the efficacy of stem cell therapy from drug therapies
Co-administration
Pre-conditioning
Route of transfusion
Treatment modalities: doses and duration
Therapeutic road map differ between autologous or allogeneic (off the shelf) cell products
Company name | Cell types | Therapeutic programs/product name | Clinical area | Reference |
---|---|---|---|---|
Aastrom Bioscience | Autologous | Multicellular therapy (Ixmyelocel-T)
| Cardiovascular disease | [121] |
Peripheral artery Diseases (PAD) | ||||
Cytomedix | Autologous adult stem cells |
ALDHbr (autologous regenerative cell therapy utilizing proprietary ALDH Bright Cell technology to isolate biologically active pluri-potent stem cells for therapeutic use) | Ischemic heart failure | [122] |
Ischemic Stroke | ||||
Critical limb ischemia | ||||
Peripheral artery Diseases (PAD) | ||||
Cytori Therapeutics | Autologous adult adipose derived stem cells |
Celution 800/CRS system (The system automates and standardizes the extraction and concentration of patients own Adipose Derived Regenerative Cells (ADRCs) in a clinical setting, enabling real-time access to autologous medical grade cells ADRCs | Acute MI | [123] |
Cardiac failure | ||||
Burn care | ||||
Regenerative cells produced utilizing proprietary | Soft tissue injury | |||
Orthopedics | ||||
Breast reconstruction | ||||
Sports medicine | ||||
Dendreon | Autologous cellular immunotherapy |
Provenge (sipuleucel-T) Body's own immune cells are isolated and reprogrammed to attack advanced prostate cancer. | Prostate cancer (asymptomatic/minimally symptomatic metastatic castrate) | [124] |
Fibrocell Science | Autologous Fibroblasts |
Azficel-T s BLA Program
| Skin | [125] |
Intrexon Synthetic Biology Rare Disease Program (Autologous cellular product treat rare and serious skin and connective tissue diseases and conditions) | Connective tissue diseases | |||
Immuno cellular therapeutics | Autologous dendritic cell |
ICT- 107 (newly diagnosed Glioblastoma) | Glioblastoma multiforme | [126] |
ICT- 121 (Recurrent Glioblastoma) | Ovarian cancer | |||
ICT- 140 (Ovarian cancer) | Cancer stem cells | |||
Autologous dendritic cell based vaccines | ||||
Japan Tissue Engineering Company (J-TEC) | Autologous cell |
Autologous cultured epidermis
| Burns | [127] |
Autologous cultured Cartilage
| Cartilage defects | |||
Autologous cultured Corneal Epithelium (Tissue engineering using autologous cells) | Corneal damage | |||
Northwest Biotherapeutics | Autologous dendritic cells |
DCVax technology (Autologous dendritic cell-based therapy) | Glioblastoma multiforme (brain tumor) | [128] |
Prostate cancer | ||||
Pharmicell | Autologous bone marrow derived MSCs |
Hearticellgram (Autologous bone marrow derived MSCs) | Acute Myocardial Infarction | [129] |
Advanced Cell Technology | Allogeneic adult stem cells hESC-derived cells |
Retinal Pigment Epithelial Cell Program for: Stargardt's macular dystropy (SMD) | Retinal Degenerative Conditions | [130] |
Dry Age-Related Macular Degeneration (AMD) | Blood and cardiovascular diseases | |||
Hemangioblast (HG) Program for: Diseases and disorders of circulatory and vascular system | ||||
Athersys | Allogeneic adult stem cells |
Multistem
| Inflammatory & Immune | [131] |
Neurological | ||||
Cardiovascular disease | ||||
Ulcerative colitis | ||||
Ischemic stroke | ||||
BioTime | Clinical-grade human embryonic stem (hES) cell lines |
OpRegen (hESC-derived RPE cells for the treatment of macular degeneration) | Age-related degenerative disease | [132] |
OPC1 (hESC-derived oligodendrocyte progenitors for spinal cord injury); | Spinal cord injury | |||
VAC1 (a dendritic cell-based vaccine for cancer based on the telomerase antigen) | Neuroscience orthopedics blood and vascular diseases oncology | |||
Medipost | Allogeneic human umbilical cord blood and Umbilical Cord Blood derived Mesenchymal Stem Cells (hUCB-MSCs) |
Cartistem (cartilage defect) | Cartilage defects | [133] |
Neurostem (neuro-degenerative disorders) | Alzheimer's disease | |||
Pneumostem (pulmonary disorders) | Amyotrophic Lateral Sclerosis (ALS) | |||
Promostem (early engraftment of donor hematopoietic stem cells (HSCs)) | Stroke | |||
Chronic lung disease (premature babies) | ||||
Mesoblast | Allogeneic adult derived mesenchymal precursor cells (MPCs) |
Proprietary Mesenchymal stem cells lineage technology
| Systemic diseases with underlying inflammatory and immunologic etiology | [134] |
Mesenchymal stem cells (MSCs) | Cardiac and vascular diseases | |||
Dental pulp stem cells (DPSCs) | Orthopedic diseases of spine | |||
Hematopoietic stem cells (HSCs) | Improving outcome of bone marrow transplantation | |||
Neostem | Autologous adult stem cells, |
Targeted Immuno Therapy Program
| Cancer treatment | [135] |
Allogeneic T cell Embryonic like stem cells & Progenitor Cells |
CD34 cell program
| Ischemic repair | ||
T Regulatory Cell Program
| Immune modulation | |||
VSEL (Very small embryonic like stem cells ) technology
| Tissue regeneration | |||
NeuralStem | Human hippocampus Neural Stem cells | NSI-189 (a compound developed for oral administration for psychiatric and cognitive disorders) | Amyotrophic Lateral Sclerosis (ALS) | [136] |
Traumatic brain injury | ||||
Alzheimer's disease | ||||
Osiris Therapeutics | Autologous and Allogeneic Mesenchymal stem cells (MSCs) |
OvationOS (bone matrix designed for the filling of bony voids and to support bone repair and regeneration) | Bone damage | [137] |
Soft tissues(cartilage and tendon) wound healing | ||||
Grafix ( Allogeneic MSCs in extracellular matrix) | ||||
Cartiform (3-dimensional architecture of hyaline cartilage that contains the necessary cellular and molecular components for articular cartilage repair, and is primed for mesenchymal stem cell (MSC) activity) | ||||
Pluristem therapeutics | Allogeneic cells |
PLX (Placental expanded cells) | Cardiovascular disease | [138] |
Orthopedic disease | ||||
Pulmonary diseases | ||||
Stemcells | Allogeneic tissue derived adult stem cells and progenitor cells |
HuCNS-SC (human neural stem cells) | Spinal cord injury | [139] |
hLEC (human liver engrafting cells) | Peripheral artery Diseases (PAD) | |||
Pelizaeus-Merzbacher Disease (PMD) | ||||
Age-related macular degeneration (AMD) | ||||
Tigenix | Autologous and Allogeneic adult stem cells |
ChondroCelect (Autologous Chondrocytes) | Cartilage defects | [140] |
eASCs (Allogeneic expanded stem cells extracted from adipose tissue ) | Perianal fistulas | |||
Rheumatois arthritis |
Pharmaceutical drug therapeutic lessons translatable and not translatable to stem cell therapies
Future perspective of stem cell therapy in regenerative medicine
Functional therapeutic approaches | Therapeutic strategies | Benefits/outcomes | Problems to be addressed |
---|---|---|---|
Co-administration
| Multiple cell types | Utilization of cell heterogeneity | Utilization of correct combinations |
Genetically engineered cells | |||
Combinations of progenitors | |||
Cytokines | Exploiting cell signalling synergistically | Understanding cell signalling for effective cell formulations | |
Growth factors | |||
Transcription factors | |||
Pre-conditioning
| Chemical (drugs) | Cyto-protection | Developing safer reprogramming & programming methods |
Physical Stimuli (hypoxia, electrical stimulation, ultrasound) | Better cell survival | ||
Genetic | Increased differentiation potential | ||
Small molecules | Enhanced paracrine effects | Understanding the mechanisms triggering the cytoprotective and other signalling pathways in response to preconditioning stimuli | |
Pre-coating | Efficient homing & integration | ||
Route of transfusion/translation
| Local or systemic | Targeted delivery | Developing efficient labelling for cell tracking post transplantation |
Intracranial, intranasal, circulatory system | Better cell survival & integration post transplantation | Complexity of multiple route delivery mechanisms | |
Intra-arterial, intra venous, cerebrospinal fluid by lumbar puncture | Understanding the migratory properties & migratory behaviour of cells through different delivery routes | ||
Doses & Durations
| Cell dose based on MSCs sources | Minimize side effects by fixed dose | Determine the potential cell source for transplantation |
Single or multiple infusion | Preventing cell lose | Determine the dose associated efficacy of allogeneic/autogenic/cryopreserved MSCs |