Vaijayanti Kale



Our Area of Research is focused on Microenvironment-mediated regulation of stem cell fate



Research Projects

  1. Effect of Simvastatin-treatment on post-irradiation recovery of hematopoiesis

  2. Hypoxic niche-mediated regeneration of hematopoiesis in the engraftment window

  3. Context-dependent Effect of Neuropilin-1 on the regulation of HSC Fate

  4. Effect of constitutively activated AKT in stromal cells on the functionality of hematopoietic stem cells co-cultured with them

  5. Identification of aging-induced epigenetic changes causing hematopoietic stem cell dysfunction: Rescue using in vitro niche (IVN)-technology

  6. Regulation of hematopoietic stem cells via nitric oxide-mediated signaling

  7. The role, and mechanism, of Free Radical Scavengers and / or Cell Death Cascade regulators in mitigating the Diabetes Mellitus-induced Endothelial Progenitor Cell (EPC) Dysfunction

  8. A study to determine the safety and efficacy of extra-cellular matrix (ECM) embedded bone marrow-derived endothelial progenitor cells (EPCs) in treatment of impaired wound healing


Translational Research Programs:

Infusion of autologous Mesenchymal Stem Cells rendered into an Artificial Bone Marrow Environment (ABME) in vitro during autologous hematopoietic stem cell transplantations.

Application of autologous Mesenchymal Stem Cells rendered into an Artificial Bone Marrow Environment (ABME) in vitro in diabetic wound healing.

These program have been approved for phase I/II clinical trials.


Research Details

1. Simvastatin improves post-irradiation hematopoiesis by preventing radiation-induced adipogenic response and radio-protecting the HSC-niche

Pre-transplant myeloablation increases marrow adipogenesis and destroys hematopoietic stem cell (HSC)-niche cells, resulting in the formation of a highly unfavorable micro-environment for the donor HSCs to home, engraft and proliferate. This becomes a serious issue when the donor HSCs are limited in number or possess compromised functionality. Here we show that Simvastatin positively affects HSC engraftment by two principal mechanisms; first, by prevention of the radiation-provoked marrow adipogenesis, and second, by affording radio-protection to the niche cells. Interestingly, Simvastatin-treatment of un-irradiated mice also boosts their HSC numbers by remodeling the niche. These data provide evidence that Simvastatin can be used as an effective niche-targeting agent to augment the donor cell engraftment and to boost the stem cell numbers in patients suffering from bone marrow failure syndromes. As Simvastatin is already a widely-used drug, clinical application of this approach might be relatively straightforward.

2. Hypoxic niche-mediated regeneration of hematopoiesis in the engraftment window is dominantly affected by oxygen tension in the milieu

The bone marrow (BM) microenvironment or the hematopoietic stem cell (HSC) niche is normally hypoxic, which maintains HSC quiescence. Paradoxically, transplanted HSCs proliferate rapidly in this niche. Pre-transplant myelo-suppression results in a substantial rise in oxygen levels in the marrow microenvironment due to reduced cellularity and consequent low oxygen consumption. Therefore, it may be construed that the rapid proliferation of the engrafted HSCs in the BM niche is facilitated by the transiently elevated oxygen tension in this milieu during the “engraftment window”. To determine whether oxygen tension dominantly affects the regeneration of hematopoiesis in the BM niche, we created an “oxygen-independent hypoxic niche” by treating BM-derived mesenchymal stromal cells (BMSCs) with a hypoxia-mimetic compound, cobalt chloride (CoCl2) and co-cultured them with BM-derived HSC-enriched cells under normoxic conditions (HSCs; CoCl2-co-cultures). Co-cultures with un-treated BMSCs incubated under normoxia (control co-cultures) or hypoxia (1% O2; hypoxic co-cultures) were used as comparators. Biochemical analyses showed that though, both CoCl2 and hypoxia evoked comparable signals in the BMSCs, the regeneration of hematopoiesis in their respective co-cultures was radically different. The CoCl2-BMSCs supported robust hematopoiesis, while the hypoxic-BMSCs exerted strong inhibition. The hematopoiesis-supportive ability of CoCl2-BMSCs was abrogated if the CoCl2-co-cultures were incubated under hypoxia, demonstrating that the prevalent oxygen tension in the milieu dominantly affects the outcome of the HSC-BM niche interactions. Our data suggest that pharmacologically delaying the re-establishment of hypoxia in the BM may boost post-transplant regeneration of hematopoiesis.


3. Context-dependent Effect of Neuropilin-1 on the Regulation of HSC Fate

Hematopoietic stem cell (HSC) fate is determined by the complex microenvironment surrounding them. This microenvironment – “the HSC niche” – comprises of various types of cells along with the cytokines secreted by them and extracellular matrix molecules. As Neuropilin 1 (NRP1) is expressed by various cell types present in the HSC niche, we postulated that NRP1 may have a regulatory effect on the HSC fate. We found that primary bone marrow-derived mesenchymal stromal cells express NRP1 after adipogenic as well as osteogenic differentiation. This result prompted us to examine whether NRP1 has any role in the regulation of hematopoiesis, and if so, whether its role depends on the cell type expressing it. In order to address this issue, we generated clones of mesenchymal stromal cell line, M210B4, stably expressing NRP1. We found M210B4 cells expressing NRP1 enhanced the proliferation and engraftment potential of HSCs co-cultured with them. Adipocytes are known to exert a negative role in the development of hematopoiesis and are responsible for the high levels of NRP1 present in the fatty marrow compared to the hematopoietically active red marrow. Using ShRNA-mediated silencing approach, we found that NRP1 actively participates in the inhibitory action of adipocytes on hematopoiesis by affecting survival and migration properties of HSCs. Our data reveal a context-dependent effect of NRP-1 on hematopoietic system.


4. Constitutive activation of AKT in stromal cells compromises engraftment ability of hematopoietic stem cells co-cultured with them

AKT pathway plays an important role in various biological processes such as cell proliferation, differentiation, etc. AKT1 and AKT2 have been shown to be critical regulators of long term functionality of hematopoietic stem cells (HSCs). On the other hand, a constitutive activation of AKT depletes HSC pool and also becomes a cause of neoplastic transformation. The consequences of constitutive activation of AKT in stromal cells on the HSC fate are, however, not known. Using murine bone marrow-derived stromal cell line genetically modified to express a constitutively active form of AKT1 we show that the HSCs co-cultured with these cells expand in numbers, but show a severe defect in their engraftment capacity due to elevated ROS levels and degradation of CXCR4 and Bmi1 mRNA in them. We further show that the stromal cells having activated AKT1 show an increase in intercellular transfer of molecular cargo to the adjoining cells, suggesting the involvement of such processes in the observed phenomenon. On the other hand, the stromal cells modified with AKT1-specific shRNA supported HSC proliferation and also boosted their engraftment capacity by enhancing the expression of CXCR4 and Bmi1 in them. These shAKT-expressing cells showed a vastly reduced intercellular transfer of molecular cargo. Our data show that the stromal cells having constitutive activation of AKT1 affect HSC functionality, possibly involving intercellular transfer mechanisms.

5. Identification of aging-induced epigenetic changes causing hematopoietic stem cell dysfunction: Rescue using in vitro niche (IVN)-technology

Establishment of in vitro-equivalents of HSC-niche is crucially important to study the molecular mechanisms involved in the regulation of stem cells via micro-environmental cues. Using mesenchymal stem cells (MSCs), we have created 3-dimensional hydrogel-based cultures of MSCs that closely mimic the in vivo HSC-niche by recapitulating several unique features of the marrow microenvironment-like formation of hypoxia-gradient, presence of SDF1α-CXCR4 axis, formation of ECM- and integrin-rich environment etc. (Sharma et al, Hematologica 2012). Using this “physiologically relevant cellular platform”, hereafter referred to as “in vitro niches (IVNs)”, we plan to study the molecular mechanisms involved in aging-mediated changes in stem cell functions. The formulations of IVNs showing desired effects on the HSC function may be eventually applied in the clinical settings for in vitro manipulation of the HSCs to improve their functions. Hematopoietic stem cells (HSCs) are the oldest and the best characterized adult stem cells. Though these cells have been used for transplantations for several decades, many aspects of their biology remain poorly understood. Since direct ex vivo manipulation of HSCs has been shown to affect their functionality, setting up of specialized regulatory in vitro niches (IVN) to improve the stem cell functions may perhaps be a safer approach.
In the present proposal we propose to identify the age-related epigenetic changes affecting HSCs function. We will then examine whether the age-related dysfunction can be reversed by using specific IVNs prepared with young MSCs or MSCs treated with specific pharmacological agents.
The HSCs harvested from old and young mice as well as the old HSCs co-cultured with young IVNs or specific signaling IVNs (under IPR) will be subjected to high throughput analyses to map their epigenetic profiles. The rescue will be assessed by performing functional assays. The study may help in gaining a clear understanding of the niche-mediated control of the stem cell fate and aid in developing customized IVNs for the in vitro modulation of stem cell functions for their optimal use in the regenerative medicine.


6. Regulation of hematopoietic stem cells via nitric oxide-mediated signaling

Haematopoiesis occurs in unique microenvironments present in the bone marrow that facilitate the maintenance of hematopoietic stem cells (HSCs) and support the maturation of progenitors. Each of these activities may require different growth factors and micro-environmental cues, the identities of which have yet to be determined. In vitro, the bone marrow stromal cells (BMSCs) serve as a rich source of growth factors for a variety of hematopoietic processes. BMSCs are composed of several different populations including fibroblasts, macrophages, endothelial cells, and adipocytes. Although it is difficult to discern the relative importance of each of these cells, it has been shown that a direct stromal cell-HSC and ECM-HSC interactions are important for regulation of haematopoiesis.
Most attempts to expand HSCs ex vivo for an enhanced in vivo engraftment in patients have been unsuccessful either because of the generation of insufficient cell numbers or due to the loss of their stem cell-specific properties as a result of the random differentiation events taking place in the culture. A right approach for an ex vivo expansion of the HSCs is to co-culture them with the components of the hematopoietic microenvironment. The mesenchymal cells (MSCs) together with the different extra-cellular matrix (ECM) components and various cytokines secreted by them form one of the principle components of the HSC microenvironment. The cell-cell interaction between the MSCs and the HSCs as well as the interactions between the HSC and the ECM components are crucial to expand the HSCs in vitro.
Although several studies have examined the role of nitric oxide in haematopoiesis, the effect of NO on HSC functionality in a concentration-dependent manner and in the context of niche has not been studied. In the present proposal, we aim to investigate the effect of NO on the fate of HSCs, especially in the context of their homing and engraftment potential. The outcome of this research will help in designing strategies for ex vivo manipulation of HSCs for increasing their engraftment potential The data obtained in the project may help in ex vivo manipulation of HSCs to enhance stem cell engraftment in transplant patients, especially when the number of stem cells are limiting in number (e.g. cord blood samples) or possess compromised functionality (e.g. stem cells isolated from older donors).


7. The role, and mechanism, of Free Radical Scavengers and / or Cell Death Cascade regulators in mitigating the Diabetes Mellitus-induced Endothelial Progenitor Cell (EPC) Dysfunction

Diabetes mellitus (DM) is a group of chronic heterogeneous metabolic disorders with increasing worldwide prevalence. Some of the hall marks of DM are pancreatic necrosis, beta cell dysfunction as well as endothelial progenitor cell dysfunction. Beta cell dysfunction is the inability of beta cells to produce / secrete insulin in response to glucose stimulus. Endothelial Progenitor Cell Dysfunction is characterized by the inability of these cells to migrate to the site of wound / ischemia / trauma and cause revascularization of the wound patch – thereby retarding the rate of wound healing. Like all other secondary complications associated with DM, the EPC dysfunction can also be attributed to hyperglycemia and enhanced oxidative stress. This condition activates many intracellular pathways that coincide with the hyperglycemia- and insulin resistance-stimulated pathways, thus compounding the damage. All of these effectively jeopardize the endogenous vascular repair in the pancreas as well as in other body parts – possibly leading to further secondary complications.
Since the primary causes of diabetes-induced EPC dysfunction are oxidative stress, insulin resistance, NFκB over-activation and cell death cascade activation, treatment with ROS scavengers and / or NFκB inhibitors may prevent / retard progressive EPC dysfunction. We will first establish the validity of two long standing models, the high-glucose induced endothelial dysfunction model and the diabetes mellitus induced in vivo endothelial dysfunction model, so as to be able to correctly extrapolate mouse data to human conditions. Logically, the prevention or reversal of EPC dysfunction may positively affect the overall vascularization process in diabetic secondary complications and diabetic wounds in general and regeneration of new islets – in particular.
Hence, it would be interesting to study the effect of ROS scavenging and / or NFkB inhibiting compounds on EPC dysfunction in diabetic mice and the mechanism thereof. Secondarily, the involvement of microRNA in these cellular events has been outlined by several groups and hence it will be of special interest to understand weather differential regulation or silencing of microRNA plays a role in the modus operandi of these compounds.

8. A study to determine the safety and efficacy of extra-cellular matrix (ECM) embedded bone marrow-derived endothelial progenitor cells (EPCs) in treatment of impaired wound healing

Diabetes mellitus (DM) is a group of chronic metabolic disorders typically characterized by hyperglycemia and widespread endothelial dysfunction leading to various secondary complications. Endothelial Progenitor Cells (EPCs) contribute to neovascularization and homeostasis of the vasculature and effective migration of the same causes efficient wound healing(1,2). Impaired migration ability, and / or capacity to incorporate into the normal wound healing process or the process of neo-vascularization, of these cells is broadly termed as endothelial dysfunction. DM-induced endothelial dysfunction may arise due to several causative factors such as reduced nitric oxide (NO) bioavailability, impaired redox balance, insulin resistance, and hyperglycemia, all of which translate into secondary complications; including impaired wound healing, one of the most debilitating consequences of endothelial dysfunction (3-8).
However, the effects of defective endothelial functions can be reversed /repaired/rescued by transplantation of EPCs from non-diabetic sources such as bone marrow, peripheral blood etc. This consequently, promises to be an effective mode of therapy. Effective and sustained delivery of normal EPCs to the wound sites poses a challenge. Current systems allow large bolii of cells to be delivered ectopically onto the wound bed. The efficacy of this system decreases as many cells are ‘lost-in-transit’ through nutrition deprivation-induced cell death or through ‘flow-away’ mechanisms. Various synthetic extra-cellular matrices fabricated from biocompatible polymers have been investigated for this purpose, each having its own advantages and limitations. Our objectives were to test for a matrix that allows growth and maintenance of EPCs and allows efficient and / or sustained delivery of these to wound site.



Extra Mural Funding

Extra Mural Funding

  1. The role, and mechanism, of Free Radical Scavengers and / or Cell Death Cascade regulators in mitigating the Diabetes Mellitus-induced Endothelial Progenitor Cell (EPC) Dysfunction (DBT - ongoing)
  2. A study to determine the safety and the efficacy of extra-cellular matrix (ECM)-embedded bone marrow-derived endothelial progenitor cells (EPCs) in the treatment of impaired wound healing. (BRNS - ongoing)
  3. Effect of hematopoiesis-regulatory factors/signaling molecules expressed in the stromal cells on the fate of the HSCs interacting with them - (DBT - completed)
  4. Creation of an in vitro model of the BM niche and studies on its impact on the Hematopoietic Stem Cells - (DBT- completed)
  5. Detection of Minimal Residual Disease in acute Leukemia by Molecular Methods - (DBT - completed)
  6. Identification of signaling mechanisms involved in the regulation of hematopoietic stem cells (HSCs) - (DBT - completed)
  7. Stem Cell Biology: Harnessing the potential of multipotent adult stem cells Development of three-dimensional cultures with mesenchymal cells to examine their effect on development of hematopoietic cells - ( DBT-completed)
  8. Identification of biochemical pathways involved in the Hematopoietic Stem Cell (HSC) regulation - (DBT- completed)
  9. Identification of molecular mechanisms involved in the adipogenic conversion of hematopoietic cells by mannose specific dietary lectins namely, banana lectin and garlic lectin - (DBT-completed)
  10. Assessment of Caveolin-1 Mutations as Possible Risk Factors in the Development of Human Breast Carcinoma - (DST-completed)


Patents and Technologies

Dr. Vaijayanti Kale

1] ‘Creation of an “Artificial Bone Marrow micro Environment (ABME) and uses thereof’ (patent jointly with TIFR, Mumbai)

Granted: Australia : 2005328537;  New Zealand : 560813;   Korea : 2007-7020266;   ARIPO : AP/P/2007/00416;  Japan : 2007-557602;  Singapore : Patent no: 134945;   Indian Patent No: 247460
Pending: Europe : 05759972.2;   U.S.A.: 11/817,173;   Canada : 2,598,936;   Brazil: PI 0518543-2;  Israel: 185516;   China: 200580048925.2
(Abstract)

 

Abstract:
Artificial Bone marrow Environments (ABME) is a platform technology comprising of mesenchymal stem cells (MSCs) cultured under proprietary conditions, which can be developed into products useful in therapeutic as well as non-therapeutic applications.

(i) Therapeutic applications:

  • Accelerated engraftment of Stem cells in SCT/BMT protocols

  • Stimulation of endogenous stem cell pool  in BM failure syndromes

  • Stem cell therapeutics in non-hematological disorders

  • Rejuvenation of aging stem cells and tissues

Therefore, we can formulate a kit for preparation of ABME from MSCs so that the clinics can themselves prepare ABME for therapeutic purposes. We may need to get some pre-clinical studies done with it, though I have done some.

(ii) Non-therapeutic applications:

  • Drug Screening – drug discovery as well as toxicity testing

  • Identification of niche defects in various disorders

  • Development of novel stem cell assays

  • Quality control for stem cell and Niche functions

 

2]  "Polycaprolactone - gelatin electrospun nanofibre matrix entrapped whole cell secretome for healing of various skin disorders and as substrate for cell attachment"

IPA no. 1951/MUM/2014.
Date of filing: 17/06/2014  (Patent filed in collaboration with IIT, Mumbai)

Abstract:
These are novel cell secretome protein compositions. Electro-spun nano-fiber matrix is seeded with Bone Marrow Progenitor Cells/ Bone Marrow and Peripheral Blood derived Cells (BMPCs). Post culturing, the secretome(s), having hydrogel-like consistency are harvested. These secretomes can be applied like salves and have excellent capacity for healing of non-healing wounds, including diabetic wounds and ulcers. They were also found to be beneficial in improving hair growth on damaged skin areas or sites of skin injury. These secretomes can be kept frozen without any loss in activity for long periods.

 

3]  "Electrospun nano-fiber scaffold (ENS)-grown blood/marrow-derived precursor cells (BMPCs) for repair of skin lesions."

 

IPA no. 3343/MUM/2012.
Date of filing: 22/11/2012. (Patent filed in collaboration with IIT, Mumbai)

 

Abstract:
The present invention is a bandage style application device made from a novel bio-compatible nano-fiber electro-spun matrix, seeded with and able to support human as well as murine bone marrow- or human peripheral blood-derived progenitor cells, including endothelial progenitor cells (EPCs). These easy to handle, one step growth and delivery-compatible bandage devices accelerate the rate of wound healing in non-healing wounds upon application. These ready-to-use bandages can be cryopreserved and used when required.

 

 

4] TECHNOLOGY:   Use of 3-dimensional cultures of MSCs for screening the molecules or substances affecting hematopoiesis

We have published this work and have shown that this in vitro system closely mimics the in vivo HSC niche. Therefore, it is an ideal system for screening various molecules, drugs etc. for their possible hematopoiesis regulatory activity. This system can also be used to determine the bone marrow toxicity of drugs, thereby reducing the number of animals used.
(There is no patent on this)

 

5] TECHNOLOGY:  MSC secretome for diabetic wound healing and reversal of diabetic hyperglycemia

  • We have developed a method to trap MSC secretome in a gel-like preparation. We have data that show that this secretome is very useful in diabetic wound healing. In fact this can be applied as a gel to any dermal wound for a scar-free wound healing, and thus, has immense potential in clinics. We have all in vivo and in vitro data using murine system. We have generated such secretome from human source as well.

  • This secretome can be preserved at -80°C without losing any activity and can be used later, making it an “off-the-shelf” product. Further experiments will be needed to examine whether this can be lyophilized without losing its activity.

  •  We also have some preliminary results showing that this secretome given intra-peritoneally brings about sustained normoglycemia in diabetic mice.

 

Dr. Vaijayanti Kale / Dr. Lalita Limaye

 

1]  “Method for preservation of human hematopoietic stem or progenitor cells”

US patent No: US 8859282 B2 (granted)
Singapore patent number 167894 (granted: 8th Aug 2014; Application number 201009450-6 dated 21st Dec 2010)
Patent No: 246982; Indian Patent Application No.: 3284/DEL/2005 (Patentee: IISc, Bangalore); Grant Date: 23-Mar-2011


Abstract:
Maintenance of quiescent hematopoietic stem and progenitor cells (HSPC) in culture without the addition of exogenous growth factors is an important aspect in clinical hematology. A recent report described the ability of Flt3 receptor-interacting lectin (FRIL) in the maintenance of cord blood (CB) derived progenitors in vitro. Since FRIL is a mannose binding lectin, the effectiveness of four such lectins of well-characterized specificities on the preservation of HSPC of CB origin have been examined. The HSPC preservation activity of lectins was assessed by in vitro colony forming unit (CFU) and long-term culture initiating cell (LTC-IC) assays. It was found that all four lectins had a HSPC preservation activity at least up to 30 days in culture without addition of exogenous growth factors. The results indicate that use of such lectins may provide a cost effective method of HSPC maintenance for clinical use.

 

*  RELATED TECHNOLOGY:   Use of Mannose-binding lectins

  • Use of plant lectins, namely Banana Lectin (BL) and Garlic lectin (GL) to preserve human hematopoietic stem progenitor cells (HSPCs):

  • This work has been published. Besides using the lectins for preservation of HSPCs, these can be used to develop CD34+ cell isolation kits as we have shown that both lectins bind to CD34+ cells.

  • Two products are anticipated from this technology, one is to develop a stem cell preservation medium and the second is to develop a CD34 cell isolation or enrichment kit.

  • These two lectins induce adipogenic conversion of MSCs and thus can be used as a screening assay for compounds affecting adipogenesis.

 

 

Publications

  1. ARTICLE IN NATURE INDIA- BONE MARROW IN TEST TUBE Click Here

  2. Manmohan Bajaj, Suprita Ghode, Rohan Kulkarni, Lalita Limaye and Vaijayanti Kale (2015) Simvastatin improves hematopoietic stem cell engraftment by preventing irradiation-induced marrow adipogenesis and radio-protecting the niche cells. Haematoloica. In press

  3. Moirangthem Ranjita Devi, Shweta Singh, Ashwini Adsul, Sapana Jalnapurkar,Lalita Limaye, and Vaijayanti P. Kale* (2015) Hypoxic niche-mediated regeneration of hematopoiesis in the engraftment window is dominantly affected by oxygen tension in the milieu. Stem Cells and Development, In press

  4. Shweta Singh, Suprita Ghode, Moirangthem Ranjita Devi, Lalita Limaye and Vaijayanti Kale (2015) Phenotypic and functional characterization of a marrow-derived stromal cell line, M210B4 and its comparison with primary marrow stromal cells. Biomedical research Journal. 2(1):120-133

  5. Vaidya A and Kale V (2015) Hematopoietic stem cells, their niche and the concept of co-culture systems: A critical review. Journal of Stem Cells, Vol 10 (1) :13-31

  6. Vaidya A and Kale V (2015) TGF–β signaling and its role in the regulation of hematopoietic stem cells. Systems and Synthetic Biology DOI 10.1007/s11693-015-9161-2 (In press).

  7. Meghana Kanitkar and Vaijayanti Kale (2014) Stem Cells and Extra Cellular Matrices: Applications in Tissue Engineering. Invited review. Biomedical Research Journal (BRJ). 1(2):95-107

  8. Meghana Kanitkar , Amit Jaiswal , Rucha Deshpande , Jayesh Bellare , Vaijayanti P. Kale. Enhanced growth of Endothelial Precursor Cells on PCG-matrix facilitates accelerated, fibrosis-free, wound healing: A diabetic mouse model. Plos One In press

  9. Roli M. Misra, Manmohan S Bajaj and Vaijayanti P. Kale (2012) Vasculogenic Mimicry of HT1080 Tumour Cells In Vivo: Critical Role of HIF-1a-Neuropilin-1 Axis. Plos One 7(11) e50153

  10. Monika Sharma, Lalita Limaye and Vaijayanti Kale (2012) Mimicking the functional hematopoietic stem cell niche in vitro: recapitulation of marrow physiology by hydrogel-based three-dimensional cultures of mesenchymal stromal cells. Haematologica. 97(5): 651-660

  11. Manmohan Bajaj, Ashwini Hinge, Lalita S. Limaye, Rajesh Kumar Gupta, Avadhesha Surolia and Vaijayanti P. Kale (2011) Mannose-binding dietary lectins induce adipogenic differentiation of the marrow-derived mesenchymal cells via an active insulin-like signaling mechanism. Glycobiology – 21(4):521-529

  12. Sangeeta V M, Vaijayanti P. Kale and Lalita S. Limaye (2010) Expansion of  Cord Blood CD34+ Cells in Presence of zVADfmk and zLLYfmk Improved Their In Vitro Functionality and In Vivo Engraftment in NOD/SCID Mouse.  PLoS ONE Aug 2010

  13. Ashwini S.Hinge, Lalita S. Limaye, Avadhesha Surolia  and Vaijayanti P. Kale (2010)   In vitro protection of umbilical cord blood-derived primitive hematopoietic stem progenitor cell pool by mannose-specific lectins via anti-oxidant mechanisms, Transfusion 50(8):1815-26.

  14. Ashwini Hinge, Manmohan Bajaj, Lalita Limaye, Avadhesha Surolia and Vaijayanti Kale (2010) Oral administration of insulin receptor-interacting lectins leads to an enhancement in the hematopoietic stem and progenitor cell pool of mice. Stem Cells and Development 19(2):163-74

  15. Balan S., V. P. Kale and L.S. Limaye (2010) A large number of mature and functional Dendritic Cells can be efficiently generated from umbilical cord blood-derived mononuclear cells by a simple two step culture method. Transfusion – 50,2413-2423

  16. Balan S., V. P. Kale and L.S. Limaye (2009): A simple two step culture system for the large scale generation of mature and functional dendritic cells from umbilical cord blood CD34+ cells.  in “Transfusion.”. 49,2109-2121

  17. Nikhat Firdous A Siddiue, Marata Shabrani, Vaijayanti Kale and Lalita Limaye (2011) Enhanced generation of megakaryocytes from umbilical cord bood-derived CD34+ cells expanded in the presence of two neutraceuticals, docosahexanoic acid and arachidonic acid, as supplement to the cytokine-containing medium Cytotherapy In press.13(1):114-128

  18. Vaidya A. A. Monika B. Sharma and Kale V. P. (2008) Suppression of p38-stress kinase sensitizes quiescent leukemic cells to anti-mitotic drugs by inducing proliferative responses in them. Cancer Biology and Therapy 7 (8):1232-40.[Link]

  19. Kale V. P. (2005) MAP Kinase: A switch in Fate Determination of Stem Cells. Stem Cells and Development. 14: 248- 251.

  20. Sasnoor Lalita, Vaijayanti Kale and Lalita Limaye(2005) Prevention of apoptosis as a possible mechanism   behind   improved cryoprotection of hematopoietic cells by catalase and trehalose. Transplantation 80:1251-1260.[Link

  21. Sasnoor Lalita, Vaijayanti Kale and Lalita Limaye (2005) A combination  of catalase and trehalose as additives in the conventional freezing medium results in improved cryoprotection of human hematopoietic cells with reference to in vitro migration and adhesion properties.  “Transfusion” 45:622-633.[Link]

  22. Kale V. P. and Vaidya A. A.  (2004) Molecular mechanisms behind the dose dependent differential activation of MAPK pathways induced by TGFβ1 in hematopoietic cells. Stem Cells and Development 13: 536-547.[Link]

  23. Kale V. P. (2004) Differential activation of MAPK signaling pathways by TGFβ1 forms the       molecular mechanism behind its dose dependent bi-directional effects on hematopoiesis. Stem Cells and Development 13:27-38.[Link]

  24. Sasnoor LM, Kale VP, Limaye LS. (2003) Supplementation of conventional freezing medium with a combination of catalase and trehalose results in better protection of surface molecules and  functionality of hematopoietic cells. J Hematother Stem Cell Res. Oct,12(5):553-64.[Link]

  25. Raju GM, Guha S, Mukhopadhyay A, Kumar L, Kale VP, Mittal S, Deka D, Mohanty S, Kochupillai V. (2003) Colony-stimulating activity of fetal liver cells: synergistic role of stem cell factor in bone marrow recovery from aplastic anemia. J Hematother Stem Cell Res.  Oct;12(5):491-7.[Link]

  26. Limaye LS, Kale VP.(2001) Cryopreservation of human hematopoietic cells with membrane stabilizers and    bioantioxidants as additives in the conventional freezing medium. J Hematother Stem Cell Res. Oct;10(5):709-18. [Link]

  27. Kale VP, Limaye LS. (1999) Stimulation of adult human bone marrow by factors secreted by fetal liver hematopoietic cells: in vitro evaluation using semisolid clonal assay system. Stem Cells. ;17(2):107-16. [Link]

  28. Kale V, Mandock O, Ibegbu C, Navalkar RG (1987). Studies on the antigenic specificity of Mycobacterium leprae. III. Further studies on immunological characterization. Zentralbl Bakteriol Mikrobiol Hyg [A]. Jun; 265(1-2):20-32. [Link]

  29. Mandock O, Ibegbu C, Kale V, Navalkar RG (1987). Studies on the antigenic specificity of Mycobacterium leprae. II. Immunological characterization. Zentralbl Bakteriol Mikrobiol Hyg [A]. Jun; 265(1-2):12-9.[Link]

  30. Ibegbu C, Mandock O, Kale V, Navalkar RG (1987). Studies on the antigenic specificity of Mycobacterium leprae. I. Isoelectric and chromatofocusing separation. Zentralbl Bakteriol Mikrobiol Hyg [A]. Apr; 264(1-2):67-77.[Link]

  31. Kale VP, Bapat CV. (1984). Antigeneic cross-reactivity between ICRC-bacilli and M. leprae--"in vitro" evaluation. Indian J Lepr. Apr-Jun;  56 (2) :219-31. [Link]

  32. Kale VP, Bhat AV, Bapat CV. (1984). Comparison of biochemical characterization of ICRC bacilli with M. leprae: effect of substrate alteration in the medium. Indian J Lepr. Apr-Jun; 56(2):212-8. [Link]

  33. Kale VP, Bhat AV, Bapat CV. (1984). Dopa-oxidase activity on ICRC bacilli. Indian  J Lepr. Jan-Mar; 56(1):58-62.[Link]

 

 

Special Lectures

 

  • Applications of artificial bone marrow microenvironments (ABME) in regenerative medicine. Invited for talk in 6th Annual Stem Cell Asia & Regenerative medicine congress 2013, Singapore, March 2013.

  • Modulating stem cell functions in vitro    Invited by DST to present my research work in the “Indo-Brazilian  
    Symposium on Biomedical Sciences”, held on August 29th and 30th, 2011,
    Rio De Janeiro, Brazil.

  • Stromal cell biology: Creation of in vitro niche (IVN) to modulate stem cell functions. Invited speaker for the meeting of “The Stem cell society of Singapore” Singapore, June 2011

  • Stromal cell biology: Creation of in vitro niche to regulate stem cell functions. Invited speaker in "InStem-CIRM collaborative meeting" Bangalore, March 21-22, 2011.

  • Therapeutic Potential of artificial bone marrow-like environments generated in vitro. Invited speaker in Biologic India” (Dec 1-4, 2009) Hyatt Regency, Mumbai, by  Terrapin, Singapore

  • Preservation of Cord Blood Derived Stem Cells in Culture. Invited speaker in "International Symposium on Stem Cells and Regenerative Medicine" at Reliance Life Sciences 27-28 Feb 2006

  • Plasticity of marrow-derived stem cells. Invited Speaker in International Workshop on Stem Cell Therapy in India - June 28th to June 31st 2005, CMC, Vellore

  • Invited Speaker. “Hematopoietic stem cell regulation through microenvironment-mediated signaling” Stem Cell Symposium at AIIMS, New Delhi, 26th -27th Nov 2005

 

Papers presented at professional meetings

 

 

1. A polycaprolactone - gelatine nanofibre matrix as a combined growth and delivery system for endothelial progenitor cells (EPCs) in     treatment of diabetic wounds Kanitkar Meghana and Vaijayanti Kale (2012) "Tissue Science 2012"Chicago, IL, USA

2. Three-dimensional hydrogel-based cultures of mesenchymal stem cells closely mimic the in vivo hematopoietic stem cell regulatory-niche.
Monika Sharma, Lalita Limaye and Vaijayanti P. Kale (2010)
Oral presentation at the annual meeting of International Society for Hematology and Stem cells (ISEH), Melbourne, Australia

3. Communication between Hematopoietic Stem Cells and Mesenchyme Cells is promoted by Gap junctions and Nano-ducts.
  Vaijayanti P. Kale and L. C. Padhy
Keystone symposium on Stem cell Niche interactions, April 21-26, 2009 Whistler,   Canada

4. Identification of domains of human endothelial nitric oxide synthase protein that strongly suppress tumour growth in vivo
Vasudha Lakshmanan, Roli Misra, Gunjan Mukherji, Michelle Vaz, L. C. Padhy and Vaijayanti P. Kale
100th annual meeting of American Association of Cancer Research (AACR), April 18-22 2009, Denver, Colorado, USA
(Ms. Vasudha received a travel grant of USD 2000 on the merit of the abstract)

5. Kale V.P.and Padhy L.C. 2007 “Transforming Growth Factor β1 is an Organizer of Hematopoietic Microenvironment”. Keystone Symposium on “stem cell interactions with their microenvironment” held on March2-7, 2007 at Keystone, Colorado, USA

6. Kale V.P. and Padhy L.C. 2007 “Highly  Effective Hematopoietic Microenvironments are formed by  Marrow Mesenchyme Cells by treatments  in vitro” Keystone Symposium on “Stem Cells and Cancer” held on March 2-7 2007 Keystone, Colorado, USA.

7. Smita Paranjape, Monika Sharma and Vaijayanti P. Kale (2009) Soluble Jagged-1 presented in the context of marrow stromal cells promotes proliferation of hematopoietic stem cells. Poster presentation at  50th Annual Conference of Association of Microbiologist of India (AMI), held in NCL from 15th Dec to 18th Dec 2009.

8. Vaidya A.V. and Kale V.P. Reciprocal modulation of p38 and p44/42 MAPK pathways in hematopoietic stem cells. 4th ISSCR Annual Meeting, Toranto, Ontario, Canada June 29th – July 1st, 2006.

9. Hinge A, Limaye LS, Surolia A and Kale VP Ex vivo preservation of hematopoietic stem and progenitor cells using mannose specific plant lectins 4th ISSCR Annual Meeting, Toranto, Ontario, Canada June 29th – July 1st, 2006


Appointments

  • Appointed as “Associate Editor” of the international journal “Stem Cells and Development”, published in USA  from June 2005

  • Appointed as member of the ICMR expert committee for “Stem Cell Research and Therapy”

  • Editor, Stem Cell Section, Biomedical Research Journal.

  • Chairperson Stem Cell Expert on the IC-SCRT of AFMC, Pune.

  • Stem cell expert on IC-SCRT committee of EmProCell, Navi Mumbai

  • Stem cell expert on Clinical Ethics Committee, Sahyadri Hospital, Pune.

  • DBT nominee for IBSC of Indian Institute of Toxicology.

  • Chairperson of IC-SCRT of Symbiosis School of Biotechnology (SSBS).

  • Stem Cell Expert on the IC-SCRT of JSS Medical College, Mysore.

 

 

Membership of professional bodies

Member of International Society of Experimental Hematologists

Member of International Society of Stem Cell Research (ISSCR)

Life member of Indian Association of Cell Biology

Life member of Indian Association of Biotechnology

Life member of Indian Society of Microbiologists

Lab Members

Dr. Meghana Kanitkar, Research Associate
Project : The role and mechanism of free radical scavengers and/or cell death cascade regulators in mitigating the Diabetes Mellitus induced Endothelial Progenitor Cells (EPCs) dysfunction.

Manmohan Bajaj, Ph.D. Student - DBT (SRF)
Project : Creation of an in vitro model of bone marrow niche and studies on its impact on hematopoietic stem cells.

Shweta Singh, Ph.D. Student- CSIR (JRF)
Project : Studies on microenvironment-mediated regulation of hematopoietic stem cells using 3-dimensional cultures

M.Ranjita Devi, Ph.D. Student-CSIR (JRF)
Project : Studies on the regulation of hematopoiesis by the micro-environment-mediated signalling mechanisms.

Suprita Ghode, Ph. D. Student-CSIR (JRF)
Project :Identification of signaling modulators in the bone marrow microenvironment regulating HSC fate

Rohan Kulkarni, Ph.D student- CSIR (JRF)
Project : Creation of in-vitro niches (IVNs) to understand the molecular mechanism involved in niche-mediated regulation of stem cell functions.

Sapana Jalnapurkar, Ph.D student- UGC(JRF)
Project : Modulation of mesenchymal stem cell culture to study their effect on haematopoietic stem cell function.

Sheetal Kadam, Ph.D student- CSIR (JRF)
Project: Role and mechanism of antioxidants cell death cascade regulators to rescue EPCs from Diabetes induced dysfunction 'in vivo' and 'in vitro'.

Richa Shukla, Project JRF
Project: A study to determine the safety and efficacy of Extra-cellular Matrix (ECM) embedded bone marrow derived EPCs in treatment of impaired wound healing.


Alumni/Ph.d Completed Students List

Vasudha Laxmanan-Nair

Kavita Kumari

Ashwini Hinge

Anuradha Vaidya

Monika Sharma

Roli Mishra


Project Scholar Alumni

Smita paranjape

Sneha Asai

Mithila Jogaikar

Priyanka Deka

Druvi Shah

Ashwini Adsul

Lakshmi N.

Kadambari Dixit


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