Concise Review: Translating Regenerative Biology into Clinically Relevant Therapies: Are We on the Right Path?

Abstract:

:Despite approaches in regenerative medicine using stem cells, bio-engineered scaffolds, and targeted drug delivery to enhance human tissue repair, clinicians remain unable to regenerate large-scale, multi-tissue defects in situ. The study of regenerative biology using mammalian models of complex tissue regeneration offers an opportunity to discover key factors that stimulate a regenerative rather than fibrotic response to injury. For example, although primates and rodents can regenerate their distal digit tips, they heal more proximal amputations with scar tissue. Rabbits and African spiny mice re-grow tissue to fill large musculoskeletal defects through their ear pinna, while other mammals fail to regenerate identical defects and instead heal ear holes through fibrotic repair. This Review explores the utility of these comparative healing models using the spiny mouse ear pinna and the mouse digit tip to consider how mechanistic insight into reparative regeneration might serve to advance regenerative medicine. Specifically, we consider how inflammation and immunity, extracellular matrix composition, and controlled cell proliferation intersect to establish a pro-regenerative microenvironment in response to injuries. Understanding how some mammals naturally regenerate complex tissue can provide a blueprint for how we might manipulate the injury microenvironment to enhance regenerative abilities in humans. Stem Cells Translational Medicine 2018;7:220-231.

journal_name

Stem Cells Transl Med

authors

Simkin J,Seifert AW

doi

10.1002/sctm.17-0213

subject

Has Abstract

pub_date

2018-02-01 00:00:00

pages

220-231

issue

2

eissn

2157-6564

issn

2157-6580

journal_volume

7

pub_type

杂志文章,评审
  • Efficient lentiviral transduction of human mesenchymal stem cells that preserves proliferation and differentiation capabilities.

    abstract::Long-term lentiviral transduction of human mesenchymal stem cells (hMSCs) greatly enhances the usefulness of these cells. However, such transduction currently requires the use of polybrene, which severely inhibits hMSC proliferation. In contrast, protamine sulfate at 100 μg/ml doubled transduction efficiencies without...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2012-0086

    authors: Lin P,Lin Y,Lennon DP,Correa D,Schluchter M,Caplan AI

    更新日期:2012-12-01 00:00:00

  • Rescue of an in vitro neuron phenotype identified in Niemann-Pick disease, type C1 induced pluripotent stem cell-derived neurons by modulating the WNT pathway and calcium signaling.

    abstract::Niemann-Pick disease, type C1 (NPC1) is a familial disorder that has devastating consequences on postnatal development with multisystem effects, including neurodegeneration. There is no Food and Drug Administration-approved treatment option for NPC1; however, several potentially therapeutic compounds have been identif...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2014-0127

    authors: Efthymiou AG,Steiner J,Pavan WJ,Wincovitch S,Larson DM,Porter FD,Rao MS,Malik N

    更新日期:2015-03-01 00:00:00

  • Cell Therapy for Chronic Limb-Threatening Ischemia: Current Evidence and Future Directions.

    abstract::Cell-based therapies have gained interest as a potential treatment method in cardiovascular disease in the past two decades, peripheral artery disease amongst others. Initial pre-clinical and small pilot clinical studies showed promising effects of cell therapy in peripheral artery disease and chronic limb-threatening...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.18-0025

    authors: Teraa M,Gremmels H,Wijnand JGJ,Verhaar MC

    更新日期:2018-12-01 00:00:00

  • Oral Mucosal Lamina Propria-Progenitor Cells Exert Antibacterial Properties via the Secretion of Osteoprotegerin and Haptoglobin.

    abstract:UNLABELLED:The oral cavity possesses a diverse microflora, yet recurrent infections within healthy individuals are rare. Wound healing within the buccal mucosa is preferential, potentially because of the presence of oral mucosal lamina propria-progenitor cells (OMLP-PCs). In addition to their multipotency, OMLP-PCs dem...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2015-0043

    authors: Board-Davies E,Moses R,Sloan A,Stephens P,Davies LC

    更新日期:2015-11-01 00:00:00

  • Comparative analysis of targeted differentiation of human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells reveals variability associated with incomplete transgene silencing in retrovirally derived hiPSC lines.

    abstract::Functional hepatocytes, cardiomyocytes, neurons, and retinal pigment epithelial (RPE) cells derived from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) could provide a defined and renewable source of human cells relevant for cell replacement therapies, drug discovery, toxicology te...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2012-0047

    authors: Toivonen S,Ojala M,Hyysalo A,Ilmarinen T,Rajala K,Pekkanen-Mattila M,Äänismaa R,Lundin K,Palgi J,Weltner J,Trokovic R,Silvennoinen O,Skottman H,Narkilahti S,Aalto-Setälä K,Otonkoski T

    更新日期:2013-02-01 00:00:00

  • Fos Promotes Early Stage Teno-Lineage Differentiation of Tendon Stem/Progenitor Cells in Tendon.

    abstract::Stem cells have been widely used in tendon tissue engineering. The lack of refined and controlled differentiation strategy hampers the tendon repair and regeneration. This study aimed to find new effective differentiation factors for stepwise tenogenic differentiation. By microarray screening, the transcript factor Fo...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.15-0146

    authors: Chen J,Zhang E,Zhang W,Liu Z,Lu P,Zhu T,Yin Z,Backman LJ,Liu H,Chen X,Ouyang H

    更新日期:2017-11-01 00:00:00

  • Concise review: next-generation cell therapies to prevent infections in neutropenic patients.

    abstract::High-dose chemotherapy is accompanied by an obligate period of neutropenia. Resulting bacterial and fungal infections are the leading cause of morbidity and mortality in neutropenic patients despite prophylactic antimicrobials and hematopoietic growth factor supplements. Replacing neutrophils in the patient through tr...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,评审

    doi:10.5966/sctm.2013-0145

    authors: Brunck ME,Nielsen LK

    更新日期:2014-04-01 00:00:00

  • Vascular Smooth Muscle Cells From Hypertensive Patient-Derived Induced Pluripotent Stem Cells to Advance Hypertension Pharmacogenomics.

    abstract:UNLABELLED:Studies in hypertension (HTN) pharmacogenomics seek to identify genetic sources of variable antihypertensive drug response. Genetic association studies have detected single-nucleotide polymorphisms (SNPs) that link to drug responses; however, to understand mechanisms underlying how genetic traits alter drug ...

    journal_title:Stem cells translational medicine

    pub_type: 临床试验,杂志文章

    doi:10.5966/sctm.2015-0126

    authors: Biel NM,Santostefano KE,DiVita BB,El Rouby N,Carrasquilla SD,Simmons C,Nakanishi M,Cooper-DeHoff RM,Johnson JA,Terada N

    更新日期:2015-12-01 00:00:00

  • Hierarchy of breast cancer cells: key to reverse dormancy for therapeutic intervention.

    abstract::An understanding of how cancer cells adapt dormancy would allow for targeted treatment. The current literature suggests that the cancer stem cells might be the major cells with the ability to become quiescent and to resist current drug treatment. The properties of cancer stem cells and healthy stem cells are functiona...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,评审

    doi:10.5966/sctm.2014-0013

    authors: Bliss SA,Greco SJ,Rameshwar P

    更新日期:2014-07-01 00:00:00

  • Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial.

    abstract::Acute respiratory distress syndrome (ARDS) in COVID-19 is associated with high mortality. Mesenchymal stem cells are known to exert immunomodulatory and anti-inflammatory effects and could yield beneficial effects in COVID-19 ARDS. The objective of this study was to determine safety and explore efficacy of umbilical c...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.20-0472

    authors: Lanzoni G,Linetsky E,Correa D,Messinger Cayetano S,Alvarez RA,Kouroupis D,Alvarez Gil A,Poggioli R,Ruiz P,Marttos AC,Hirani K,Bell CA,Kusack H,Rafkin L,Baidal D,Pastewski A,Gawri K,Leñero C,Mantero AMA,Metalonis SW

    更新日期:2021-01-05 00:00:00

  • Concise review: ex vivo expansion of cord blood-derived hematopoietic stem and progenitor cells: basic principles, experimental approaches, and impact in regenerative medicine.

    abstract::Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) play key roles in the production of mature blood cells and in the biology and clinical outcomes of hematopoietic transplants. The numbers of these cells, however, are extremely low, particularly in umbilical cord blood (UCB); thus, ex vivo expan...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,评审

    doi:10.5966/sctm.2013-0071

    authors: Flores-Guzmán P,Fernández-Sánchez V,Mayani H

    更新日期:2013-11-01 00:00:00

  • A Phase I Study to Assess the Safety and Cancer-Homing Ability of Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells in Men with Localized Prostate Cancer.

    abstract::Animal models show that systemically administered bone marrow-derived mesenchymal stem cells (MSCs) home to sites of primary and metastatic prostate cancer (PC)-making them candidates to selectively deliver cytotoxic agents. To further assess this potential as a cell-based therapeutic vehicle, a phase I study testing ...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.18-0230

    authors: Schweizer MT,Wang H,Bivalacqua TJ,Partin AW,Lim SJ,Chapman C,Abdallah R,Levy O,Bhowmick NA,Karp JM,De Marzo A,Isaacs JT,Brennen WN,Denmeade SR

    更新日期:2019-05-01 00:00:00

  • Multipotent mesenchymal stromal cells synergize with costimulation blockade in the inhibition of immune responses and the induction of Foxp3+ regulatory T cells.

    abstract::Multipotent mesenchymal stromal cell (MSC) therapy and costimulation blockade are two immunomodulatory strategies being developed concomitantly for the treatment of immunological diseases. Both of these strategies have the capacity to inhibit immune responses and induce regulatory T cells; however, their ability to sy...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2014-0012

    authors: Takahashi T,Tibell A,Ljung K,Saito Y,Gronlund A,Osterholm C,Holgersson J,Lundgren T,Ericzon BG,Corbascio M,Kumagai-Braesch M

    更新日期:2014-12-01 00:00:00

  • Glyoxalase-1 Overexpression Reverses Defective Proangiogenic Function of Diabetic Adipose-Derived Stem Cells in Streptozotocin-Induced Diabetic Mice Model of Critical Limb Ischemia.

    abstract::Adipose-derived stem cell (ADSC)-based therapy is promising for critical limb ischemia (CLI) treatment, especially in patients with diabetes. However, the therapeutic effects of diabetic ADSCs (D-ADSCs) are impaired by the diabetes, possibly through intracellular reactive oxygen species (ROS) accumulation. The objecti...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2015-0380

    authors: Peng Z,Yang X,Qin J,Ye K,Wang X,Shi H,Jiang M,Liu X,Lu X

    更新日期:2017-01-01 00:00:00

  • Concise Review: Organoids Are a Powerful Tool for the Study of Liver Disease and Personalized Treatment Design in Humans and Animals.

    abstract::Organoids are three-dimensional culture systems in which adult stem cells and their progeny grow and represent the native physiology of the cells in vivo. Organoids have been successfully derived from several organ systems in both animal models and human patients. Organoids have been used for fundamental research, dis...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,评审

    doi:10.5966/sctm.2015-0152

    authors: Nantasanti S,de Bruin A,Rothuizen J,Penning LC,Schotanus BA

    更新日期:2016-03-01 00:00:00

  • Concise review: stem/progenitor cells for renal tissue repair: current knowledge and perspectives.

    abstract::The kidney is a specialized low-regenerative organ with several different types of cellular lineages; however, the identity of renal stem/progenitor cells with nephrogenic potential and their preferred niche(s) are largely unknown and debated. Most of the therapeutic approaches to kidney regeneration are based on admi...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,评审

    doi:10.5966/sctm.2013-0097

    authors: Aggarwal S,Moggio A,Bussolati B

    更新日期:2013-12-01 00:00:00

  • Comparison of Different Cytokine Conditions Reveals Resveratrol as a New Molecule for Ex Vivo Cultivation of Cord Blood-Derived Hematopoietic Stem Cells.

    abstract:UNLABELLED:Human cord blood (CB)-derived hematopoietic stem cells (HSCs) are an interesting source for HSC transplantation. However, the number of collected CB-HSCs is often too low for one transplantation; therefore, ex vivo expansion of CB-HSCs is desirable. Current expansion protocols are based on the use of cytokin...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2014-0284

    authors: Heinz N,Ehrnström B,Schambach A,Schwarzer A,Modlich U,Schiedlmeier B

    更新日期:2015-09-01 00:00:00

  • Enhancing in vivo survival of adipose-derived stromal cells through Bcl-2 overexpression using a minicircle vector.

    abstract::Tissue regeneration using progenitor cell-based therapy has the potential to aid in the healing of a diverse range of pathologies, ranging from short-gut syndrome to spinal cord lesions. However, there are numerous hurdles to be overcome prior to the widespread application of these cells in the clinical setting. One o...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2013-0035

    authors: Hyun J,Grova M,Nejadnik H,Lo D,Morrison S,Montoro D,Chung M,Zimmermann A,Walmsley GG,Lee M,Daldrup-Link H,Wan DC,Longaker MT

    更新日期:2013-09-01 00:00:00

  • Proceedings: human leukocyte antigen haplo-homozygous induced pluripotent stem cell haplobank modeled after the california population: evaluating matching in a multiethnic and admixed population.

    abstract::The development of a California-based induced pluripotent stem cell (iPSC) bank based on human leukocyte antigen (HLA) haplotype matching represents a significant challenge and a valuable opportunity for the advancement of regenerative medicine. However, previously published models of iPSC banks have neither addressed...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2015-0052

    authors: Pappas DJ,Gourraud PA,Le Gall C,Laurent J,Trounson A,DeWitt N,Talib S

    更新日期:2015-05-01 00:00:00

  • Cancer Stem Cells Therapeutic Target Database: The First Comprehensive Database for Therapeutic Targets of Cancer Stem Cells.

    abstract::Cancer stem cells (CSCs) are a subpopulation of tumor cells that have strong self-renewal capabilities and may contribute to the failure of conventional cancer therapies. Hence, therapeutics homing in on CSCs represent a novel and promising approach that may eradicate malignant tumors. However, the lack of information...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2015-0289

    authors: Hu X,Cong Y,Luo HH,Wu S,Zhao LE,Liu Q,Yang Y

    更新日期:2017-02-01 00:00:00

  • Lung Injury Repair by Transplantation of Adult Lung Cells Following Preconditioning of Recipient Mice.

    abstract::Repair of injured lungs represents a longstanding therapeutic challenge. We recently demonstrated that human and mouse embryonic lung tissue from the canalicular stage of development are enriched with lung progenitors, and that a single cell suspension of canalicular lungs can be used for transplantation, provided tha...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.17-0149

    authors: Milman Krentsis I,Rosen C,Shezen E,Aronovich A,Nathanson B,Bachar-Lustig E,Berkman N,Assayag M,Shakhar G,Feferman T,Orgad R,Reisner Y

    更新日期:2018-01-01 00:00:00

  • Immature Midbrain Dopaminergic Neurons Derived from Floor-Plate Method Improve Cell Transplantation Therapy Efficacy for Parkinson's Disease.

    abstract::Recent reports have indicated human embryonic stem cells-derived midbrain dopamine (mDA) neurons as proper cell resources for use in Parkinson's disease (PD) therapy. Nevertheless, no detailed and systematic study has been conducted to identify which differentiation stages of mDA cells are most suitable for transplant...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.16-0470

    authors: Qiu L,Liao MC,Chen AK,Wei S,Xie S,Reuveny S,Zhou ZD,Hunziker W,Tan EK,Oh SKW,Zeng L

    更新日期:2017-09-01 00:00:00

  • Humanized culture of periosteal progenitors in allogeneic serum enhances osteogenic differentiation and in vivo bone formation.

    abstract::The translation of stem cell-based regenerative solutions from the laboratory to the clinic is often hindered by the culture conditions used to expand cell populations. Although fetal bovine serum (FBS) is widely used, regulatory bodies and safety concerns encourage alternative, xeno-free culturing practices. In an at...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2012-0137

    authors: Roberts SJ,Owen HC,Tam WL,Solie L,Van Cromphaut SJ,Van den Berghe G,Luyten FP

    更新日期:2014-02-01 00:00:00

  • Sustained knockdown of a disease-causing gene in patient-specific induced pluripotent stem cells using lentiviral vector-based gene therapy.

    abstract::Patient-specific induced pluripotent stem cells (iPSCs) hold great promise for studies on disease-related developmental processes and may serve as an autologous cell source for future treatment of many hereditary diseases. New genetic engineering tools such as zinc finger nucleases and transcription activator-like eff...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2013-0017

    authors: Eggenschwiler R,Loya K,Wu G,Sharma AD,Sgodda M,Zychlinski D,Herr C,Steinemann D,Teckman J,Bals R,Ott M,Schambach A,Schöler HR,Cantz T

    更新日期:2013-09-01 00:00:00

  • Cross talk between mesenchymal and glioblastoma stem cells: Communication beyond controversies.

    abstract::Mesenchymal stem cells (MSCs) can be isolated from bone marrow or other adult tissues (adipose tissue, dental pulp, amniotic fluid, and umbilical cord). In vitro, MSCs grow as adherent cells, display fibroblast-like morphology, and self-renew, undergoing specific mesodermal differentiation. High heterogeneity of MSCs ...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章,评审

    doi:10.1002/sctm.20-0161

    authors: Bajetto A,Thellung S,Dellacasagrande I,Pagano A,Barbieri F,Florio T

    更新日期:2020-11-01 00:00:00

  • Osteogenic Stimulation of Human Adipose-Derived Mesenchymal Stem Cells Using a Fungal Metabolite That Suppresses the Polycomb Group Protein EZH2.

    abstract::Strategies for musculoskeletal tissue regeneration apply adult mesenchymal stem/stromal cells (MSCs) that can be sourced from bone marrow- and lipo-aspirates. Adipose tissue-derived MSCs are more easily harvested in the large quantities required for skeletal tissue-engineering approaches, but are generally considered ...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.17-0086

    authors: Samsonraj RM,Dudakovic A,Manzar B,Sen B,Dietz AB,Cool SM,Rubin J,van Wijnen AJ

    更新日期:2018-02-01 00:00:00

  • Directing Differentiation of Pluripotent Stem Cells Toward Retinal Pigment Epithelium Lineage.

    abstract::Development of efficient and reproducible conditions for directed differentiation of pluripotent stem cells into specific cell types is important not only to understand early human development but also to enable more practical applications, such as in vitro disease modeling, drug discovery, and cell therapies. The dif...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2016-0088

    authors: Choudhary P,Booth H,Gutteridge A,Surmacz B,Louca I,Steer J,Kerby J,Whiting PJ

    更新日期:2017-02-01 00:00:00

  • Optimized serial expansion of human induced pluripotent stem cells using low-density inoculation to generate clinically relevant quantities in vertical-wheel bioreactors.

    abstract::Human induced pluripotent stem cells (hiPSCs) have generated a great deal of attention owing to their capacity for self-renewal and differentiation into the three germ layers of the body. Their discovery has facilitated a new era in biomedicine for understanding human development, drug screening, disease modeling, and...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.1002/sctm.19-0406

    authors: Borys BS,So T,Colter J,Dang T,Roberts EL,Revay T,Larijani L,Krawetz R,Lewis I,Argiropoulos B,Rancourt DE,Jung S,Hashimura Y,Lee B,Kallos MS

    更新日期:2020-09-01 00:00:00

  • Epimuscular Fat in the Human Rotator Cuff Is a Novel Beige Depot.

    abstract:UNLABELLED:: Chronic rotator cuff (RC) tears are a common and debilitating injury, characterized by dramatic expansion of adipose tissue, muscle atrophy, and limited functional recovery. The role of adipose expansion in RC pathology is unknown; however, given the identified paracrine/endocrine regulation by other adipo...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2014-0287

    authors: Meyer GA,Gibbons MC,Sato E,Lane JG,Ward SR,Engler AJ

    更新日期:2015-07-01 00:00:00

  • Functional Maturation of Induced Pluripotent Stem Cell Hepatocytes in Extracellular Matrix-A Comparative Analysis of Bioartificial Liver Microenvironments.

    abstract:UNLABELLED:: Induced pluripotent stem cells (iPSCs) are new diagnostic and potentially therapeutic tools to model disease and assess the toxicity of pharmaceutical medications. A common limitation of cell lineages derived from iPSCs is a blunted phenotype compared with fully developed, endogenous cells. We examined the...

    journal_title:Stem cells translational medicine

    pub_type: 杂志文章

    doi:10.5966/sctm.2015-0235

    authors: Wang B,Jakus AE,Baptista PM,Soker S,Soto-Gutierrez A,Abecassis MM,Shah RN,Wertheim JA

    更新日期:2016-09-01 00:00:00